The correct answer is: 3. IgA nephropathy. Given that the clinical presentation of this nephropathy appears in a very unspecific way, to identify the responsible disease we must rely on its epidemiology. Since he is a young male, with a history of previous respiratory infections, a relationship between these infections and renal pathology is established. Based on this we think about IgA nephropathy, which besides being the most frequent glomerulonephritis, it is presented in most of the cases as described.

The [HIDDEN] IgA nephropathy. Given that the clinical presentation of this nephropathy appears in a very unspecific way, to identify the responsible disease we must rely on its epidemiology. Since he is a young male, with a history of previous respiratory infections, a relationship between these infections and renal pathology is established. Based on this we think about IgA nephropathy, which besides being the most frequent glomerulonephritis, it is presented in most of the cases as described.

A 35-year-old man presenting hematuria after respiratory infections for several years, a blood test shows creatinine 1 mg/dl with no other alterations and urine hematocytes 50/field being 80% dysmorphic, with proteinuria of 0.8 grams in 24 hours. What is the most likely diagnosis?

Proliferative and diffuse glomerulonephritis.

Focal and primary segmental glomerulosclerosis.

Long-term outcome of adult patients with minimal urinary abnormalities and normal renal function.

To define the long-term outcome of patients with minimal urinary abnormalities (defined by the presence of microscopic hematuria with no or less than 1 gm/day proteinuria), and normal renal function (defined by a serum creatinine < 1.3 mg/dl), we retrospectively studied patients who fulfilled the above criteria and had a kidney biopsy done before the year of 1992 (i.e. at least followed up for 5 years), with a definite pathological diagnosis. A total of 41 cases among 719 cases of primary glomerulonephritis (5.7%) were enrolled into the study. There were 19 males and 22 females with a mean age of 35.4+/-14.7 years at biopsy. The duration of renal disease was 116.0+/-60.5 months and the duration of follow-up post biopsy was 100.2+/-38.1 months. The pathological diagnosis was: IgA nephropathy (21 cases), focal glomerulosclerosis (9 cases), mesangial proliferative glomerulonephritis (8 cases), membranous glomerulonephritis (2 cases) and acute glomerulonephritis (1 case). At the end of follow-up, 8 cases (19.5%) had a certain degree of renal insufficiency including 2 (4.9%) in end-stage renal disease. The other cases were either in complete remission (6 cases) or stable condition (27 cases) with persistent microscopic hematuria and normal renal function. The long-term outcome was not correlated with any of the following parameters: age, sex, disease duration, serum creatinine at presentation, daily protein loss at presentation, degree of glomerular change and degree of interstitial inflammatory cell infiltration. However, a poor long-term outcome was correlated with tubular atrophy (p < 0.05) and interstitial fibrosis (p < 0.05). We conclude that a minimal urinary abnormality with normal renal function at presentation does not necessarily imply a favorable long-term outcome in certain patients. Tubular atrophy and interstitial fibrosis but not glomerular change correlates with a worse prognosis. This further emphasizes the importance of renal biopsy in such cases.

[Clinicopathological correlation of young onset chronic glomerulonephritis].

In a retrospective analytical study involving 98 children with primary glomerulonephritis who were seen by us at our hospital during a 2-year period from 1984 through 1985 and who had renal biopsy performed previously, attempts were made to correlate pathological findings with both clinical findings and prognosis. The results are summarized as follows: 1) Of 87 patients with asymptomatic chronic glomerulonephritis, glomerular findings were those of minimal change lesion, mesangial proliferative nephritis, MPGN, membranous nephropathy and FGS or sclerosing nephritis in 29.9%, 51.7%, 13.8%, 1.1% and 3.5%, respectively. Among the other 11 patients in whom the diagnosis was made after manifesting the nephritic symptoms, minimal change was noted less frequently and MPGN was detected more frequently than in the aforementioned asymptomatic group. IgA nephropathy was estimated to account for 44.2% of cases of asymptomatic chronic nephritis. 2) Mild mesangial proliferation was observed relatively frequently and severe mesangial proliferation or MPGN rather infrequently in hematuria cases without proteinuria while in those with severe proteinuria minimal change lesion was uncommon and severe mesangial proliferative changes, MPGN or FGS were relatively frequent. 3) In 22 patients with IgA nephropathy and 11 with non-IgA nephritis the severity of glomerular changes was related to the intensity of proteinuria at the time of renal biopsy. 4) A 3 to 5 years' follow-up study of patients with mesangial proliferative nephritis inclusive of IgA nephropathy disclosed that 26-28% of patients became free from urinary abnormalities, 27-37% had persistent hematuria without proteinuria and 24-32% still had proteinuria of 2 plus or above. Patients with milder glomerular changes had a definitely better prognosis than those with severe glomerular lesions.

Crescentic IgA nephropathy.

We report five cases of crescentic IgA nephropathy. All are males, 16-60 years of age. One case each came to medical attention with uremia, nephrotic syndrome, and gross hematuria; two cases presented with microhematuria and proteinuria on routine urinalysis. All had hypertension, azotemia (serum creatinine 1.6-9.4 mg/dl), proteinuria (greater than 6 g/24 hr in four cases), hypoalbuminemia (less than 3 g/dl), and hematuria (gross in two cases). All progressed to end-stage renal failure renal failure ending in dialysis (three cases) or death from unrelated causes (two cases). Prednisone, 60 mg/day for 1 month in two patients (with two 1-g doses of iv methylprednisolone in 1 case) did not improve the serum creatinine level, but one patient subsequently experienced a less rapid fall in renal function. A crescentic glomerulonephritis was present in all biopsies (crescents in 31-80% of glomeruli; mean, 50%). The size and stage of the crescents were variable. Numerous glomeruli had focal or diffuse sclerosis. In all cases, there was a 3 or 4+ deposition of IgA. Low-intensity staining for IgG and IgM was noted in four and three patients, respectively. On electron microscopy, dense granular mesangial deposits were noted in all cases and in four patients capillary subepithelial deposits were also observed. This form of IgA nephropathy is not common, but some studies indicate that it may occur in about 5% of patients with IgA nephropathy.

Berger's disease in children. Natural history and outcome.

The clinical course and outcome of 91 children less than 15 years of age at onset and followed for at least 1 year have been retrospectively analyzed. The course has been characterized by recurrent macroscopic hematuria in 74 patients, by proteinuria-microscopic hematuria and a single episode of macroscopic hematuria occurring either at onset or a few months later in 8, by proteinuria-microscopic hematuria in 7, and by proteinuria only in 1. Lastly, one patient showed rapidly progressive renal failure. Four groups were identified by light microscopy: minimal glomerular changes (26), focal and segmental glomerulonephritis (41), pure mesangial proliferation (3) and proliferative glomerulonephritis with crescents (21). A good correlation was found between the glomerular lesions observed by light microscopy and the outcome. In this series we have not observed a dramatic clinical deterioration suggesting a transformation from one histologic type to another, as reported by others. None of the 70 patients belonging to the first three groups has impaired renal function but two with focal and segmental glomerulonephritis have developed hypertension. Although the clinical course is benign, many patients have, at the last observation, an abnormal urinalysis characterized by microscopic hematuria and/or mild proteinuria; the proteinuria is over 1 g/24 h in six patients with focal and segmental glomerulonephritis. Ten patients remained in clinical remission for several years, but mesangial IgA deposits were still present in the only patient who had a repeat biopsy while in remission. In contrast, none of the patients with proliferative glomerulonephritis with crescents has had a prolonged remission. Six patients developed terminal renal failure 0.7, 0.11, 2, 4, 8 and 10 years after onset. Two additional patients are in moderate chronic renal failure with hypertension 10 and 12 years after onset. Most children show a persistent nephropathy, (in five proteinuria is over 1 g/24 h), and two of them have developed hypertension. Therapeutic trials using drugs with side-effects should, therefore, be used only in this group of patients.

[A case of childhood IgA nephropathy who developed rapidly progressive glomerulonephritis in one-year clinical course].

A 10-year-old girl who presented with microscopic hematuria, proteinuria and normal renal function has been followed up for the past two years. At the first examination, renal biopsy revealed focal/segmental lesions accompanying by occaisional necrosis and small crescents. Diagnosis of IgA nephropathy was given by light, electron and immunofluorescent microscopic findings. She started on the treatment with dipyridamol and was followed up for one year without any serious complications. Thereafter, she suddenly developed severe deterioration of renal function (serum creatinine 2.7 mg/dl) with nephrotic syndrome and hypertension. The second renal biopsy done at this time indicated the presence of typical crescentic glomerulonephritis with mesangial proliferation. No vasculitis was noted. She was intensively treated with steroids, anticoagulants and other medication and responded fairly well clinically. The third renal biopsy performed 5 months afterwards demonstrated marked histological improvement, but there was still present mesangial proliferation and varied degrees of sclerotic changes with fibrocellular crescents. Focal interstitial fibrosis and collapsed tubules were also seen. At present, 5 months after the last renal biopsy, she has improved much better and her serum creatinine decreased to 1.9 mg/dl, although proteinuria of 3 g/day still persists. It is suggested that only a small segmental necrosis with crescent formation in IgA nephropathy should be considered as an important indicator of disease activity in the evaluation of prognosis.

Clinical outcomes and predictors for ESRD and mortality in primary GN.

Relatively little is known about the long-term outcomes of different histologic types of primary glomerulonephritis in Asian populations. From 1993 to 2006, 987 patients undergoing renal biopsy were studied, and 580 patients (mean age=44.4 years, male=58.5%) with the four most common forms of glomerulonephritis (membranous nephropathy, focal and segmental glomerulosclerosis, IgA nephropathy, and minimal change disease) were selected for analysis. Median follow-up period was 5.9 (interquartile range=5.7) years. The focal and segmental glomerulosclerosis group displayed the highest incidence of ESRD (25.8%) and the fastest decline of estimated GFR (4.6 ml/min per 1.73 m(2) per year). The IgA nephropathy group also had a higher rate of ESRD than the membranous nephropathy patients (19.2% versus 4.3%, P<0.001). In contrast, the membranous nephropathy group exhibited an overall death rate similar to the focal and segmental glomerulosclerosis group (17.2% versus 14.4%) but higher than the IgA nephropathy and minimal change disease patients (4.6% and 3.7%, respectively, P<0.001). The most powerful predictor for ESRD was focal and segmental glomerulosclerosis, whereas the strongest predictor for all-cause mortality was membranous nephropathy with higher proteinuria. Protectors against ESRD included male sex and higher hemoglobin. Most predictors for ESRD and overall mortality found in this ethnic Chinese cohort were similar to other studies. However, some risk factors linked with distinct glomerular pathologies displayed differential clinical outcomes.

Renal biopsy findings and clinical indicators of patients with hematuria without overt proteinuria.

Whether to perform a renal biopsy for isolated hematuria remains a matter of controversy. We performed renal biopsy in hematuria without overt proteinuria patients and reported the proportion of glomerulonephritis, pathological activities, and statistical analysis of indicators associated with glomerulonephritis. Among 203 patients who underwent renal biopsy in Okubo Hospital, Japan, between January 2008 and October 2013, we identified 56 patients who fulfilled the criteria: (1) urine dipstick examination shows equal to or greater than ± blood on three or more visits, (2) proteinuria <0.3 g/day (g/g Cr), (3) eGFR ≧60 ml/min/1.73 m(2), and (4) no current medication for renal disease. We investigated biopsy findings and compared the clinical indicators in the IgA nephropathy (IgAN) and non-IgAN group. The pathological diagnosis was IgAN in 35 cases (62 %), thin basement membrane disease (TBMD) in 7 (13 %), minor glomerular abnormality (MGA) in 6 (11 %), glomerular basement membrane (GBM) abnormality in 5 (9 %), and others in 3 (5 %). The histological grade of IgAN was I in 90 % and II in 10; 31 % of patients had some crescentic lesions. Comparisons between the IgAN and non-IgAN group revealed significant differences in age of onset (26 ± 13 vs. 34 ± 17 years, p = 0.04), serum IgA (340 ± 114 vs. 220 ± 101 mg/dl, p < 0.01), proteinuria (0.08 [0-0.25] vs. 0 [0-0.23] g/day [g/gCr], p < 0.01), and the presence of poikilocytes (40 vs. 10 %, p = 0.02). The proportion of IgAN in hematuria without overt proteinuria was high and the pathological activities were variable. Patients with hematuria without overt proteinuria should continue their medical follow-up and the best timing of biopsy may be controversial for these patients who have multiple risk factors of IgAN.

IgA nephropathy

For an adult patient with isolated hematuria, tests such as ultrasound of the kidney and cystoscopy are usually done first to pinpoint the source of the bleeding. These tests would rule out kidney stones and bladder cancer, two other common urological causes of hematuria. In children and younger adults, the history and association with respiratory infection can raise the suspicion of IgA nephropathy. A kidney biopsy is necessary to confirm the diagnosis. The biopsy specimen shows proliferation of the mesangium, with IgA deposits on immunofluorescence and electron microscopy. However, patients with isolated microscopic hematuria (i.e. without associated proteinuria and with normal kidney function) are not usually biopsied since this is associated with an excellent prognosis. A urinalysis will show red blood cells, usually as red cell urinary casts. Proteinuria, usually less than 2 grams per day, also may be present. Other renal causes of isolated hematuria include thin basement

Development of anti-glomerular basement membrane glomerulonephritis during the course of IgA nephropathy: a case report.

Anti-glomerular basement membrane (GBM) glomerulonephritis does not usually coexist with another glomerulonephritis such as IgA nephropathy. We present a rare case having a combination of these two diseases, and furthermore, histological evaluation could be performed before and after the development of anti-GBM glomerulonephritis over a period of only10 months. A 66-year-old woman was admitted with complaints of microscopic hematuria and mild proteinuria for the past 3 years. Serum creatinine level was normal at that time. The first renal biopsy was performed. Light microscopy revealed mesangial proliferative glomerulonephritis with fibro-cellular crescents in one out of 18 glomeruli, excluding one global sclerotic glomerulus. Immunofluorescence (IF) showed IgA and C3 deposition in the mesangium. Therefore, the diagnosis was IgA nephropathy. Eight months later, the patient's serum creatinine suddenly rose to 4.53 mg/dL and urinalysis showed 100 red blood cells per high power field with nephrotic range proteinuria (12.3 g/g<subCr</sub). The serological tests revealed the presence of anti-GBM antibody at the titer of 116 IU/mL. Treatments were begun after admission, consisting of hemodialysis, plasma exchange, and intravenous methylprednisolone pulse therapy. At 4 weeks after admission, the second renal biopsy was performed. Light microscopy revealed crescents in 18 of 25 glomeruli, excluding six global sclerotic glomeruli. IF showed linear IgG deposition along the GBM in addition to granular IgA and C3 deposition. Based on these findings, the diagnosis of anti-GBM glomerulonephritis and IgA nephropathy was confirmed. Renal function was not restored despite treatment, but alveolar hemorrhage was prevented. We report a patient with a diagnosis of anti-GBM disease during the course of IgA nephropathy. This case strongly suggests that the presence of autoantibodies should be checked to rule out overlapping autoimmune conditions even in patient who have previously been diagnosed with chronic glomerulonephritis, such as IgA nephropathy, who present an unusually rapid clinical course.

Glomerulonephritis

Proliferative Proliferative glomerulonephritis is characterised by an increased number of cells in the glomerulus. These forms usually present with a triad of blood in the urine, decreased urine production, and hypertension, the nephritic syndrome. These forms usually progress to end-stage kidney failure (ESKF) over weeks to years (depending on type). IgA nephropathy IgA nephropathy, also known as Berger's disease, is the most common type of glomerulonephritis, and generally presents with isolated visible or occult hematuria, occasionally combined with low grade proteinuria, and rarely causes a nephritic syndrome characterised by protein in the urine, and visible blood in the urine. IgA nephropathy is classically described as a self-resolving form in young adults several days after a respiratory infection. It is characterised by deposits of IgA in the space between glomerular capillaries.

IgA nephropathy

A smaller proportion (20–30%), usually the older population, have microscopic hematuria and proteinuria (less than 2 gram/day). These patients may be asymptomatic and only picked up due to urinalysis. Hence, the disease is more commonly diagnosed in situations where screening of urine is compulsory (e.g., schoolchildren in Japan). Very rarely (5% each), the presenting history is: Nephritic syndrome Acute kidney failure (either as a complication of the frank hematuria, when it usually recovers or due to rapidly progressive glomerulonephritis which often leads to chronic kidney failure) Chronic kidney failure (no previous symptoms, presents with anemia, hypertension and other symptoms of kidney failure, in people who probably had longstanding undetected microscopic hematuria and/or proteinuria)

Kidney disease

IgA nephropathy IgA nephropathy is the most common glomerulonephritis throughout the world Primary IgA nephropathy is characterized by deposition of the IgA antibody in the glomerulus. The classic presentation (in 40-50% of the cases) is episodic frank hematuria which usually starts within a day or two of a non-specific upper respiratory tract infection (hence synpharyngitic) as opposed to post-streptococcal glomerulonephritis which occurs some time (weeks) after initial infection. Less commonly gastrointestinal or urinary infection can be the inciting agent. All of these infections have in common the activation of mucosal defenses and hence IgA antibody production. Iodinated contrast media

The kidney biopsy is foundational to informing the diagnosis of mesangial proliferative glomerulonephritis, as it is a morphological pattern. Clinical Presentation Mesangial proliferative glomerulonephritis often presents with hematuria (gross or microscopic) or nephrotic syndrome. Presentation can also include asymptomatic proteinuria. These presenting symptoms are relatively non-specific and are often seen in other glomerular disorders. Preceding upper respiratory tract infection or post-streptococcal glomerulonephritis may contribute to hematuria, as both have been identified in patients presenting with hematuria in the context of mesangial proliferative glomerulonephritis. Preceding infection was not as readily identified in patients presenting with either asymptomatic proteinuria or nephrotic syndrome. However, it is has been shown patients presenting with nephrotic syndrome have some histo- and clinic-pathologic similarities to minimal change disease.

Nephritic syndrome

Children/adolescents IgA nephropathy (Note: Contrast time of onset with Post-streptococcal Glomerulonephritis) - Most commonly diagnosed in children who recently had an upper respiratory tract infection (URI). Symptoms typically present within 1–2 days of a non-specific URI with severe flank/abdominal pain, gross hematuria (characterized by dark brown or red colored urine), and edema of the hands, feet, and/or face. Post-streptococcal glomerulonephritis (PSGN) - Similar to IgA nephropathy, post-streptococcal glomerulonephritis (PSGN) most often occurs in children who have recently had an upper respiratory infection (URI). In contrast with IgA nephropathy, however, PSGN typically presents 2–3 weeks after recovering from an URI that was caused specifically by a Streptococcus bacteria. The symptoms at onset are very similar to IgA nephropathy and include abdominal pain, hematuria, edema, and oliguria.

Nephrotic syndrome

Epidemiology Nephrotic syndrome can affect any age, although it is mainly found in adults with a ratio of adults to children of 26 to 1. The syndrome presents in different ways in the two groups: the most frequent glomerulopathy in children is minimal change disease (66% of cases), followed by focal segmental glomerulosclerosis (8%) and mesangiocapillary glomerulonephritis (6%). In adults the most common disease is mesangiocapillary glomerulonephritis (30-40%), followed by focal and segmental glomeruloesclerosis (15-25%) and minimal change disease (20%). The latter usually presents as secondary and not primary as occurs in children. Its main cause is diabetic nephropathy. It usually presents in a person from their 40s or 50s. Of the glomerulonephritis cases, approximately 60% to 80% are primary, while the remainder are secondary. There are also differences in epidemiology between the sexes, the disease is more common in men than in women by a ratio of 2 to 1.

Changes in the diagnosis of glomerular diseases in east China: a 15-year renal biopsy study.

There have been some gradual changes in the distribution of renal biopsy pathological diagnoses during recent years. This study aimed to show changes in renal disease prevalence in China by investigating 10 patients diagnosed at our Kidney Disease Centre during the last 15 years. All patients aged 15-year-old or older who underwent renal biopsy at the First Affiliated Hospital, Zhejiang University, from 2001 to 2015 were enrolled. There were 5 common types of primary glomerulonephritis: IgA nephropathy (IgA N), membranous nephropathy (MN), mesangial progressive glomerulonephritis (MsPGN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS), which represented 50%, 16.8%, 15.9%, 8.1% and 2.5% of total cases, respectively. IgA nephropathy was the most common type of primary glomerulonephritis (PGN). Our results mostly showed a new trend that the diagnosis of IgA nephropathy was not increasing and the prevalence of membranous nephropathy had increased, becoming the second most common type of primary glomerulonephritis. Key POINTS Distinguished with other domestic studies, IgA nephropathy did not show a trend of continuous growth although it still had about the half proportion of PGN, whereas membranous nephropathy kept rising and became the second common PGN. Concerning SGN, LN peaked in the younger-age and middle-age groups with a significant female prevalence, DN, BANS and SV had a male predominance peaking in the middle-age and old-age groups.

A case of minimal change nephrotic syndrome with immunoglobulin A nephropathy transitioned to focal segmental glomerulosclerosis.

A 50-year-old woman with a 1-month history of lower extremity edema and a 5 kg weight increase was admitted to our hospital with suspected nephrotic syndrome in October 1999. Urine protein level was 3.5 g per day, 10-15 erythrocytes in urine per high-power field, and serum albumin level 2.5 g/dl. Furthermore, an accumulation of pleural effusion was confirmed by chest X-ray. The results of a renal biopsy indicated slight mesangial proliferation in the glomeruli by light microscopy, and an immunofluorescence study confirmed the deposition of immunoglobulin (Ig) A and C3 in the mesangial area. Diffuse attenuation of foot processes and dense deposits in the mesangial area were observed by electron microscopy. Treatment with 40 mg/day of prednisolone was effective, and proteinuria was negative 1 month later. Because of this course, we diagnosed minimal change nephrotic syndrome complicated by mild-proliferative IgA nephropathy. In November 2000, there was a relapse of nephrotic syndrome, which was believed to be induced by an influenza vaccination, but response to increased steroid treatment was favorable, and proteinuria disappeared on day 13 of steroid increase. A second relapse in May 2001, showed steroid resistance with renal insufficiency, and an increase in the selectivity index to 0.195. Light microscopy revealed focal sclerotic lesions of the glomeruli, and an immunofluorescence study revealed attenuation of mesangial IgA and C3 deposition. These findings led to the diagnosis that minimal change nephrotic syndrome had transitioned to focal segmental glomerulosclerosis, whereby mesangial IgA deposition was reduced by immunosuppressive treatment. Subsequently, her renal function gradually worsened to the point of end-stage renal failure by 27 months after the second relapse of nephrotic syndrome.

Increasing incidence of focal segmental glomerulosclerosis and an examination of demographic patterns.

Idiopathic focal segmental glomerulosclerosis (FSGS) is one of the leading causes of the nephrotic syndrome in adults and an important cause of end-stage renal disease. Its incidence has dramatically increased in the last two decades and it is especially prevalent among black patients. The trend of FSGS incidence has not been reported beyond 1997. We retrospectively reviewed all renal biopsies performed at our institution between 1986 and 2002 and identified patients with diagnoses consistent with primary glomerulopathy (PG), which included: minimal-change disease (MCD), idiopathic focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MGN), IgA nephropathy (IgA), membrano-proliferative glomerulonephritis (MPGN) and mesangioproliferative glomerulonephritis. Patients with possible secondary causes for their renal disease were excluded. Clinical data at the time of biopsy and follow-up data were collected and analyzed. During the period from January 1986-December 2002, 299 renal biopsies were performed and 132 patients were diagnosed with PG. FSGS was the most common form of PG representing 37.8% of all PG followed by IgA 27.3%, MGN 16.6% and MCD 9.1%. Among FSGS patients 59% were females, 64% had nephrotic range proteinuria and 54% had the nephrotic syndrome. Mean serum creatinine was 2.0 +/- 0.2 mg/dl and mean protein excretion was 6.1 +/- 1.0 g/day. The incidence of FSGS increased from 19.3% (1986-1991) and 16.6% (1992-1997) to 58.5% in the period from 2002. The increase occurred among black and Hispanic patients (33.3-79.2%) as well as white patients (12.5-51.5%). Black and Hispanic patients with PG presented for renal biopsy at a significantly younger age than white patients (p = 0.003), with mean age 37.5 +/- 2.0 years vs. 50.3 +/- 1.8 years. White FSGS patients were significantly older than white non-FSGS patients (mean age 56.4 +/- 3.2 years vs. 48.0 +/- 2.0 years, p = 0.03). Black and Hispanic FSGS patients were also older when compared to their non-FSGS counter-parts (mean age 40.6 +/- 2.8 years vs. 32.1 +/- 2.0 years, p = 0.04). When patients were stratified by age (< 45 years and > or = 45 years), FSGS was the most common diagnosis in both age groups among black and Hispanic patients (55.1% and 88.8%) but only among older white patients (36.2%). The incidence of FSGS as a proportion of PG in our population has increased markedly in the most recent time period analyzed (1998-2002). The increase has occurred among both white and black and Hispanic patients. We also found that FSGS was most prevalent in patients > or = 45 years.

Membranous glomerulonephritis

Within membranous glomerulonephritis, especially in cases caused by viral hepatitis, serum C3 levels are low. Similar to other causes of nephrotic syndrome (e.g., focal segmental glomerulosclerosis or minimal change disease), membranous nephropathy is known to predispose affected individuals to develop blood clots such as pulmonary emboli. Membranous nephropathy in particular is known to increase this risk more than other causes of nephrotic syndrome though the reason for this is not yet clear.

InternalMed_Harrison

The two most common presentations of IgA nephropathy are recurrent episodes of macroscopic hematuria during or immediately following an upper respiratory infection often accompanied by proteinuria or persistent asymptomatic microscopic hematuria. Nephrotic syndrome is uncommon. Proteinuria can also first appear late in the course of the disease. Rarely patients present with acute renal failure and a rapidly progressive clinical picture. IgA nephropathy is a benign disease for the majority of patients, and 5–30% of patients may go into a complete remission, with others having hematuria but well preserved renal function. In the minority of patients who have progressive disease, progression is slow, with renal failure seen in only 25–30% of patients with IgA nephropathy over 20–25 years. This risk varies considerably among populations. Cumulatively, risk factors for the loss of renal function identified thus far account for less than 50% of the variation in observed outcome but include

Minimal change disease and IgA deposition: separate entities or common pathophysiology?

Introduction. Minimal Change Disease (MCD) is the most common cause of nephrotic syndrome in children, while IgA nephropathy is the most common cause of glomerulonephritis worldwide. MCD is responsive to glucocorticoids, while the role of steroids in IgA nephropathy remains unclear. We describe a case of two distinct clinical and pathological findings, raising the question of whether MCD and IgA nephropathy are separate entities or if there is a common pathophysiology. Case Report. A 19-year old man with no medical history presented to the Emergency Department with a 20-day history of anasarca and frothy urine, BUN 68 mg/dL, Cr 2.3 mg/dL, urinalysis 3+ RBCs, 3+ protein, and urine protein : creatinine ratio 6.4. Renal biopsy revealed hypertrophic podocytes on light microscopy, podocyte foot process effacement on electron microscopy, and immunofluorescent mesangial staining for IgA. The patient was started on prednisone and exhibited dramatic improvement. Discussion. MCD typically has an overwhelming improvement with glucocorticoids, while the resolution of IgA nephropathy is rare. Our patient presented with MCD with the uncharacteristic finding of hematuria. Given the improvement with glucocorticoids, we raise the question of whether there is a shared pathophysiologic component of these two distinct clinical diseases that represents a clinical variant.

Membranous glomerulonephritis

Membranous glomerulonephritis (MGN) is a slowly progressive disease of the kidney affecting mostly people between ages of 30 and 50 years, usually white people (ie, those of European, Middle Eastern, or North African ancestry.). It is the second most common cause of nephrotic syndrome in adults, with focal segmental glomerulosclerosis (FSGS) recently becoming the most common. Signs and symptoms Most people will present as nephrotic syndrome, with the triad of albuminuria, edema and low serum albumin (with or without kidney failure). High blood pressure and high cholesterol are often also present. Others may not have symptoms and may be picked up on screening, with urinalysis finding high amounts of protein loss in the urine. A definitive diagnosis of membranous nephropathy requires a kidney biopsy, though given the very high specificity of anti-PLA2R antibody positivity this can sometimes be avoided in patients with nephrotic syndrome and preserved kidney function Causes

Association of IgA nephropathy with steroid-responsive nephrotic syndrome. A report of the Southwest Pediatric Nephrology Study Group.

In a multicenter study of 83 children with IgA nephropathy, we have encountered four patients (three female, one male) who presented with steroid-responsive nephrotic syndrome (NS) 1 to 12 years before the demonstration of IgA nephropathy. Renal biopsies performed within several months of the onset of NS in three of the patients showed changes consistent with minimal change glomerulonephropathy in two and diffuse mesangial hypercellularity in one patient. Immunofluorescence studies performed on two of the biopsies were negative for IgA. Corticosteroid therapy induced remission of NS in all four patients, but this was followed by frequent relapses. IgA nephropathy was diagnosed subsequently by renal biopsies that were performed because of the onset of gross hematuria in three patients and persistent, low-grade proteinuria in the other. Light microscopy studies on these biopsies showed minimal glomerular changes in three and focal proliferative and sclerosing glomerulonephritis in one patient. Subsequent follow-up evaluations have revealed normal serum creatinines and/or glomerular filtration rate (GFR) in all four patients with remission of NS in three and no further episodes of gross hematuria in any patient. These four patients represent either a variant of IgA nephropathy associated with long-standing steroid-responsive NS or development of IgA nephropathy superimposed upon preceding minimal change disease.

IgA nephropathy

Signs and symptoms The classic presentation for the non-aggressive form (in 40–50% of the cases) is episodic hematuria, which usually starts within a day or two of a non-specific upper respiratory tract infection (hence synpharyngitic), as opposed to post-streptococcal glomerulonephritis, which occurs some time (weeks) after initial infection. With both aggressive and non-aggressive Berger's disease loin pain can also occur. The gross hematuria may resolve after a few days, though microscopic hematuria will persist, it is however more common with aggressive Berger's disease for gross hematuria to persist rather than microscopic hematuria. Renal function usually remains normal with non-aggressive Berger's disease, though rarely acute kidney failure may occur (see below). This presentation is more common in younger adults.

Hematuria

Glomerular hematuria Glomerular causes include: IgA nephropathy Thin glomerular basement membrane disease Hereditary nephritis (Alport's disease) Hemolytic uremic syndrome Postinfectious glomerulonephritis Membranoproliferative glomerulonephritis Lupus nephritis Henoch-Shonlein purpura Nephritic syndrome Nephrotic syndrome Polycystic kidney disease Idiopathic hematuria Non-glomerular hematuria Visible blood clots in the urine indicate a non-glomerular cause. Non-glomerular causes include:

IgA Nephropathy (Berger Disease) -- History and Physical

Asymptomatic hematuria with mild proteinuria, such as 0.5 g/day, may be picked up on screening programs. A proportion of patients with isolated microscopic hematuria and mild proteinuria will ultimately develop significant proteinuria and hypertension, suggesting that long-term follow-up should be instituted. [34] Progressive chronic kidney disease is a common manifestation observed in many cohorts. Renal survival varies greatly according to biopsy timing and the introduction of lead-time bias. The actual renal 10-year survival is observed to be 57% to 91%. [35]

Berger Disease -- History and Physical

Most patients present with asymptomatic microscopic hematuria or proteinuria that can be present for many years. Hypertension is initially found in a minority of patients but becomes common as the disease progresses to chronic kidney disease or end-stage renal disease. IgA nephropathy can present with gross hematuria, nephrotic syndrome, and chronic kidney disease and can escalate to rapidly progressive glomerulonephritis. Episodic gross hematuria is commonly seen in children and young adults after upper respiratory tract infection. Synpharingitic macroscopic hematuria is a classic initial presentation of IgA nephropathy.

Proteinuria

Proteinuria may be a feature of the following conditions: Nephrotic syndromes (i.e. intrinsic kidney failure) Pre-eclampsia Eclampsia Toxic lesions of kidneys Amyloidosis Collagen vascular diseases (e.g. systemic lupus erythematosus) Dehydration Glomerular diseases, such as membranous glomerulonephritis, focal segmental glomerulonephritis, minimal change disease (lipoid nephrosis) Strenuous exercise Stress Benign orthostatic (postural) proteinuria Focal segmental glomerulosclerosis (FSGS) IgA nephropathy (i.e. Berger's disease) IgM nephropathy Membranoproliferative glomerulonephritis Membranous nephropathy Minimal change disease Sarcoidosis Alport syndrome Diabetes mellitus (diabetic nephropathy) Drugs (e.g. NSAIDs, nicotine, penicillamine, lithium carbonate, gold and other heavy metals, ACE inhibitors, antibiotics, or opiates (especially heroin) Fabry disease Infections (e.g. HIV, syphilis, hepatitis, poststreptococcal infection, urinary schistosomiasis)

[Thin glomerular membrane nephropathy. Clinico-pathological observations].

In two nephrology centres between 1983 and 1993 among 1545 kidney biopsies 34 cases of thin basement membrane nephropathy have been diagnosed. All patients had a varying degree of microscopic dysmorph haematuria, occasional slight proteinuria--except two nephrotic children; and normal blood pressure with one exception. 5 children and 7 adults experienced repeated bouts of macroscopic haematuria mainly after exercise or upper respiratory tract infection, one child after tonsillectomy. All patients had normal renal function and retained it during the follow-up period (mean 61 months, 3 months to 22 years), except a 46 year old patient, who was found to have the joint occurrence of light chain gammopathy and hypertension. Seven patients had positive family history for microscopic haematuria, in four family members of three patients renal biopsy disclosed mesangioproliferative glomerulonephritis with thin GBM segments. As a cut off value for thin basement membrane nephropathy we considered 264 nm. The morphometric analysis of the electron micrographs revealed a mean thickness of 210 nm. No differences in basement membrane thickness were measured regarding gender, age or the presence of macroscopic haematuria. The thin basement membrane is considered to be the pathological basis and predisposing alteration leading to haematuria.

Diffuse proliferative nephritis

Signs and Symptoms Symptoms can be caused directly from DPGN or from a different disease that is causing DPGN. Many of the symptoms, like edema and hypertension, occur due to the decrease in glomerular filtration rate. Patients can experience general systemic symptoms including fatigue, vomiting, nausea. These would all indicate uremia. Other patients can experience: Decreased urine output Hematuria Microscopic or gross Proteinuria Which will present as frothy urine Pedal edema Swelling of the feet and ankles DPGN caused by other diseases If a patient has DPGN due to IgA nephropathy (Berger Disease) then they can experience flank pain, gross hematuria, and upper respiratory infections. If a patient has DPGN with underlying anti-GBM then they can experience alveolar hemorrhage and respiratory issues. If a patient has DPGN with an underlying autoimmune disease then the patient can experience photosensitivity, rash, joint pains, serositis, and oral ulcers.

Acquired glomerular lesions in patients with Down syndrome.

The long-term survival of persons with Down syndrome has dramatically increased over the past 50 years. There are no studies addressing the spectrum of glomerular lesions in these patients. We reviewed the clinical-pathologic characteristics of 17 patients with Down syndrome who underwent renal biopsy. The cohort consisted of 12 whites and 5 African Americans with mean age of 29 years (range, 6-45 years). History of hypothyroidism was present in 8 patients. Renal presentations included renal insufficiency (15 patients, mean serum creatinine 3.4 mg/dL), proteinuria (all patients, including 3 with nephrotic syndrome, mean 24-hour urine protein 4.2 g), and hematuria (14 patients, including 4 with gross hematuria). The glomerular diseases found on biopsy were IgA nephropathy (n = 5 patients), focal segmental glomerulosclerosis (n = 4), membranoproliferative glomerulonephritis (n = 2), acute postinfectious glomerulonephritis (n = 2), pauci-immune crescentic glomerulonephritis (n = 2), membranous glomerulonephritis (n = 1), and lupus nephritis (n = 1). Follow-up (mean, 47 months; range, 2-141 months) was available on 16 patients (94%). Two patients (1 with membranous glomerulonephritis and 1 with acute postinfectious glomerulonephritis) had complete remission; 8 patients (4 with IgA nephropathy, 2 with focal segmental glomerulosclerosis, 1 with lupus nephritis, and 1 with acute postinfectious glomerulonephritis) had chronic kidney disease; and 6 patients (2 with pauci-immune crescentic glomerulonephritis, 2 with membranoproliferative glomerulonephritis, 1 with IgA nephropathy, and 1 with focal segmental glomerulosclerosis) progressed to end-stage renal disease, 4 of whom died. In summary, a wide spectrum of glomerular diseases can be seen in patients with Down syndrome, with IgA nephropathy and focal segmental glomerulosclerosis being the most common. Renal biopsy is necessary to determine the type of glomerular lesion and appropriate treatment.

Minimal-change glomerulopathy of adulthood.

We describe 40 adults with idiopathic minimal-change glomerulopathy. They consisted of 27 females and 13 males, mean age 40.7 +/- (SD) 19.8 years (range 15-78 years). Twenty patients were less than 40 years of age at presentation. They presented with significantly (p less than 0.05) lower serum creatinine (0.9 +/- 0.2 vs. 1.3 +/- 0.5 mg/dl) and serum albumin (1.9 +/- 0.8 vs. 2.4 +/- 0.7 g/dl) levels than patients greater than 40 years. Only 7 patients (18%) presented with a decrease in renal function (serum creatinine greater than 1.3 mg/dl). All patients had nephrotic-range proteinuria at the time of presentation or biopsy. There was no significant difference in presenting proteinuria (8.7 +/- 5.7 g/24 h) or length of follow-up (mean 63.5, range 4-176 months) between the two age groups. Microscopic hematuria and hypertension were each present in 21% of the patients. Thirty-four patients received therapy with prednisone. A complete remission was obtained in 91% of the patients treated with prednisone. The response occurred within 16 weeks in 77% of the patients. The response to prednisone therapy was similar for patients less than 40 years when compared to those greater than 40 years, with a complete remission being obtained in 88 and 94%, respectively. The rate of response, however, differed significantly with 73% of patients less than 40 years versus 32% of patients greater than 40 years achieving a complete remission by 8 weeks. Twenty patients initially responding to prednisone therapy (64.5%) relapsed. A relapse occurred within 3 months of attaining a complete remission in 70% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)


In principle, this is an easy question, as it deals with a disease that is frequently repeated in the MIR exams. The description is typical of option 2. It is an exudative AMD (although as we said in question 215, with the new classification, we would speak of an advanced AMD in its neovascular variant). In any case, we have an elderly patient with vision loss and metamorphopsia in one eye. In the examination there are lesions in the macula. With that we can rule out acute posterior vitreous detachment, which does not produce visual loss, nor metamorphopsia, nor lesions in the macula. And also non-arteritic anterior ischemic optic neuropathy, because although it produces visual loss and is typical of older people, it does not produce metamorphopsia. And there are no lesions in the macula but papilla edema. In central retinal artery obstruction, metamorphopsia is not particularly characteristic (visual loss and advanced age are), but the lesions in the fundus of the eye vary. In the case of arterial occlusion, there is intracellular edema that is seen as absence of hemorrhages and a whitish, pale fundus. In addition, the entire retina is globally affected, and a cherry-red spot may appear in the macula. In this case the lesions are totally different. They describe hard exudates, deep hemorrhages and localized neurosensory retinal detachment. All this in the macula. These are the characteristic findings of neovascular (or exudative) AMD. As a clue, in the other eye there are abundant soft drusen. Drusen are the typical findings of AMD. So he has AMD in both eyes and in the right eye it has recently become complicated by the appearance of neovascularization.

An 84-year-old woman presents with loss of vision in the left eye of 4 days of evolution accompanied by metamorphopsia. The macula shows abundant hard exudates, two small deep hemorrhages and a localized neurosensory retinal detachment. In the contralateral eye there are abundant soft drusen. Given this picture, which of the following diagnoses do you think is the most likely?

Exudative age-related macular degeneration (AMD).

Non-arteritic anterior ischemic optic neuropathy.

[Clinical and pathological observation of seven cases of spontaneous sub-retinal hemorrhage].

To improve pathological understanding of massive sub-retinal hemorrhage. Retrospective case series study. The clinical and pathological data of 7 cases of massive sub-retinal hemorrhage which were examined in the Pathological Department of Tianjin Eye Hospital from May 1988 to April 2012 were collected. The serial section of eyeball specimens were made with HE and PAS staining. The pathological section were reviewed under the light microscope. Analysis were made again combining with patients' clinical history, imaging findings and the pathological features. In 7 patients, 6 patients were male, 1 patient was female. The age range was from 60 to 82 years old and the average age was 71.7 years old. Four cases were on the right eye and 3 cases were on the left eye. The main clinical feature was sudden loss of vision and 2 cases had acute glaucoma symptoms. Ultrasound examination showed choroidal tumor in 6 cases and retinal detachment with vitreous hemorrhage in one case. The color Doppler ultrasound examination demonstrated choroidal substantive occupying lesion in 3 cases and two of them were detected with blood flow signal. The MRI were examined in 3 cases which showed iso-high signal in T1W1 and iso-low signal in T2W1 suggesting the choroidal melanoma in 2 cases and sub-retinal hemorrhage in 1 case. Six cases were diagnosed clinically as choroidal tumor or melanoma and 1 case was diagnosed as acute angle-closure glaucoma. The enucleation were performed in 7 cases. In these cases, 6 cases were diagnosed pathologically as vitreous hemorrhage, hemorrhagic RPE detachment and massive subretinal hemorrhage. The related choroidal lesions included soft drusen of Bruch membrane in 3 cases, choriocapillaris wall degeneration in 2 cases, fibrovascular membrane formation under RPE in 2 cases, choroidal chronic non-granulomatous inflammation in 4 cases, choroidal vessels wall thickening and sclerosis in 2 cases and choroidal vessels anomaly in one case. The secondary angle-closure glaucoma or angle-open glaucoma were accompanied respectively in 2 cases. Another case of 7 cases was diagnosed pathologically as the rupture of retinal macroaneurysm with massive sub-retinal hemorrhage. Massive sub-retinal hemorrhage liked to occur in the elderly male patients. The main manifestations were sudden visual loss. A small number of patients had symptoms of acute glaucoma. Ophthalmic ultrasound and imaging characteristics were usually similar to the choroidal substantive neoplasm and were easily misdiagnosed as choroidal melanoma. Pathological examination revealed that the main reasons of massive hemorrhage were from the hemorrhagic RPE detachment and the rupture of retinal macroaneurysm.

[Preventive treatment using laser of age-related macular degeneration of the contralateral eye after age-related macular degeneration of the first eye].

Since 1982, and with informed patient consent, we have photocoagulated confluent drusen and limited serous pigment epithelium detachment (SPED) in the fellow eye of ten patients suffering from advanced, disciform type, age-related macula degeneration (ARMD). This treatment was only carried out on appearance of metamorphopsia. Photocoagulation was performed with either the green ray of the argon laser, or the yellow ray of a dye laser. Spots of about 200 microns were placed in a grid-like fashion among the drusen. No complications were observed due to the treatment. The follow-up period on these ten patients, eight women and two men, mean age 77 years, was two to eight years, and the three patients have died. The drusen disappeared completely in three patients and partially in one. The functional results seemed favorable in three cases. In one case of confluent drusen associated with SPED and serous retinal detachment, vision improved remarkably from 0.3 to 0.5 with a Parinaud 2, with a follow-up of five years. In another case, the improvement was from 0.4 to 0.7 but the patient died after only a few months. In another case, vision has been stable for five years. The vision of the seven remaining patients deteriorated; three cases showed central areolar sclerosis, and one case a localised new vessel with vision less than 0.1. In three cases vision dropped to 0.2 and Parinaud 6, but they have been stable for at least four years (eight years for one patient).(ABSTRACT TRUNCATED AT 250 WORDS)

Drusen

Drusen, from the German word for node or geode (singular, "Druse"), are tiny yellow or white accumulations of extracellular material that build up between Bruch's membrane and the retinal pigment epithelium of the eye. The presence of a few small ("hard") drusen is normal with advancing age, and most people over 40 have some hard drusen. However, the presence of larger and more numerous drusen in the macula is a common early sign of age-related macular degeneration (AMD). Classification Drusen are associated with aging and macular degeneration are distinct from another clinical entity, optic disc drusen, which is present on the optic nerve head. Both age-related drusen and optic disc drusen can be observed by ophthalmoscopy. Optical coherence tomography scans of the orbits or head, calcification at the head of the optic nerve without change in size of globe strongly suggests drusen in a middle-age or elderly patient.

The causes of hyperreflective dots in optical coherence tomography excluding diabetic macular edema and retinal venous occlusion§.

To investigate the causes of hyperreflective dots (HRDs) in spectral domain optical coherence tomography (OCT) excluding diabetic macular edema (DME) and RVO (retinal vein occlusion). The medical records of 56 patients with HRDs documented by OCT were reviewed retrospectively. The patients with DME and RVO were excluded from the study in order to prevent misdiagnosing hard exudates or HRDs. The causes, unilaterality or bilaterality of HRD and demographic properties of the patients with HRD were evaluated. Sixty four eyes of 56 patients having HRDs were included in this study. Of the patients with HRD, 17 (30.36%) were women and 39 (69.64%) were men. The ages of patients were between 13 to 84 years (median 60.18 years). The causes of HRD were as follows: papilledema in 4 eyes (6.25%), active neovascular age related macular degeneration (AMD) in 33 eyes (51.56%), familial dominant drusen in 2 eyes (3.13%), central serous chorioretinopathy in 19 eyes (29.69%) and commotio retina in 2 eyes (3.13%), choroidal folds in one eye (1.56%), branch retinal artery occlusion in one eye (1.56%), central retinal artery occlusion in one patient (1.56%) and Best vitelliform macular dystrophy in one eye (1.56%). The most common cause of HRD was AMD. The causes of HRDs in both eyes were AMD and papilledema. The most common causes of HRDs excluding DME and RVO seem as active exudative AMD. The presence of HRDs in retinal diseases might affect the decisions and the results of the treatment and the prognosis of diseases.

InternalMed_Harrison

Impending branch or central retinal vein occlusion can produce prolonged visual obscurations that resemble those described by patients with amaurosis fugax. The veins appear engorged and phlebitic, with numerous retinal hemorrhages (Fig. 39-8). In some patients, venous blood flow recovers spontaneously, whereas others evolve a frank obstruction with extensive retinal bleeding (“blood and thunder” appearance), infarction, and visual loss. Venous occlusion of the retina is often idiopathic, but hypertension, diabetes, and glaucoma CHAPTER 39 Disorders of the Eye FIguRE 39-5 Hollenhorst plaque lodged at the bifurcation of a retinal arteriole proves that a patient is shedding emboli from the carotid artery, great vessels, or heart. FIguRE 39-7 Hypertensive retinopathy with blurred optic disc, scattered hemorrhages, cotton-wool spots (nerve fiber layer infarcts), and foveal exudate in a 62-year-old man with chronic renal failure and a systolic blood pressure of 220.

Acute visual loss

Acute visual loss is a rapid loss of the ability to see. It is caused by many ocular conditions like retinal detachment, glaucoma, macular degeneration, and giant cell arteritis, etc. Main causes Retinal detachment Retinal detachment should be considered if there were preceding flashes or floaters, or if there is a new visual field defect in one eye. If treated early enough, retinal tear and detachment can have a good outcome. Glaucoma Angle-closure glaucoma should be considered if there is painful loss of vision with a red eye, nausea or vomiting. The eye pressure will be very high typically greater than 40 mmHg. Emergent laser treatment to the iris may prevent blindness. Macular degeneration Wet macular degeneration should be considered in older people with new distortion of their vision with bleeding in the macula. Vision can often be regained with prompt eye injections with anti-VEGF agents. Giant cell arteritis

Wet Age-Related Macular Degeneration (Wet AMD) -- History and Physical

On examination, patients frequently have decreased best-corrected visual acuity (BCVA), and Amsler grid evaluation may reveal areas of central or paracentral scotoma or visual distortion. Ophthalmic examination of the anterior segment of the eye is usually normal. ARMD-related CNV has several different appearances on the dilated funduscopic exam. [17] These include: A gray-green membrane deep into the retina is usually associated with an overlying neurosensory retinal detachment. There may be the presence of blood, lipid, or subretinal fluid. RPE detachments appear clinically as dome-shaped, sharply demarcated elevations of the RPE; these may also be serous, fibrovascular, drusenoid, or hemorrhagic. [18] There may be massive subretinal hemorrhage with central vision loss or, less commonly, breakthrough vitreous hemorrhage with peripheral vision loss. RPE tears. Disciform scars may be present, which may appear as white or yellow subretinal membranes with or without RPE hyperplasia.

InternalMed_Harrison

Optic Disc Drusen These are refractile deposits within the substance of the optic nerve head (Fig. 39-13). They are unrelated to drusen of the retina, which occur in age-related macular degeneration. Optic disc drusen are most common in people of northern European descent. Their diagnosis is obvious when they are visible as glittering particles on the surface of the optic disc. However, in many patients they are hidden beneath the surface, producing pseudopapilledema. It is important to recognize optic disc drusen to avoid an unnecessary evaluation for papilledema. Ultrasound or computed tomography (CT) scanning is sensitive for detection of buried optic disc drusen because they contain calcium. In most patients, optic disc drusen are an incidental, innocuous finding, but they can produce visual obscurations. On perimetry they give rise to enlarged blind spots and arcuate CHAPTER 39 Disorders of the Eye

InternalMed_Harrison

FIguRE 39-9 Anterior ischemic optic neuropathy from temporal arteritis in a 67-year-old woman with acute disc swelling, splinter hemorrhages, visual loss, and an erythrocyte sedimentation rate of 70 mm/h. FIguRE 39-11 Optic atrophy is not a specific diagnosis but refers to the combination of optic disc pallor, arteriolar narrowing, and nerve fiber layer destruction produced by a host of eye diseases, especially optic neuropathies.

InternalMed_Harrison

Papilledema This connotes bilateral optic disc swelling from raised intracranial pressure (Fig. 39-12). Headache is a common but not invariable accompaniment. All other forms of optic disc swelling (e.g., 203 from optic neuritis or ischemic optic neuropathy) should be called “optic disc edema”. This convention is arbitrary but serves to avoid confusion. Often it is difficult to differentiate papilledema from other forms of optic disc edema by fundus examination alone. Transient visual obscurations are a classic symptom of papilledema. They can occur in only one eye or simultaneously in both eyes. They usually last seconds but can persist longer. Obscurations follow abrupt shifts in posture or happen spontaneously. When obscurations are prolonged or spontaneous, the papilledema is more threatening. Visual acuity is not affected by papilledema unless the papilledema is severe, longstanding, or accompanied by macular edema and hemorrhage. Visual field testing shows enlarged blind spots

InternalMed_Harrison

FIgURE 40e-3 Superficial flame-shaped hemorrhages, dot hem-orrhages, and microaneurysms in a patient with nonproliferative diabetic retinopathy. patientwithchronicleukemia. Conditions associated with retinal hemorrhages include diseases causing retinal microvasculopathy (Table 40e-3), retinitis, retinal macroaneurysm, papilledema, subarachnoid hemorrhage (Terson’s syndrome), Valsalva retinopathy, trauma (ocular injury, head injury, compression injuries of chest and abdomen, shaken baby syndrome, strangulation), macular degeneration, and posterior vitreous detachment. Hyperviscosity states may produce dot and blot hemorrhages, dilated veins (“string of sausages” appearance), optic disc edema, and exudates; similar changes can occur with adaptation to high altitude in mountain climbers.

Neurology_Adams

In persons older than 50 years of age, a common cause of a persistent monocular loss of vision is ischemic infarction of the optic nerve head (Fig. 12-15). With anterior ischemic optic neuropathy, the optic disc is involved and optic disc edema is visualized in the acute phase. In contrast, with posterior ischemic optic neuropathy, there are no changes of the optic disc until disc pallor develops in the chronic stages. Ischemic optic neuropathy can be either arteritic (discussed in the following text) or nonarteritic. With nonarteritic anterior ischemic optic neuropathy (NAION), the onset is typically abrupt and painless, but on occasion the visual loss is progressive for several days. Usually, there are no premonitory symptoms or episodes of transient visual loss. The field defect is often altitudinal. If the area of central fixation is involved, then acuity can be severely compromised. Swelling of the optic disc is typical, and can be sectoral, with certain portions of the disc

InternalMed_Harrison

Optic nerve disease produces characteristic patterns of visual field loss. Glaucoma selectively destroys axons that enter the superotemporal or inferotemporal poles of the optic disc, resulting in arcuate scotomas shaped like a Turkish scimitar, which emanate from the blind spot and curve around fixation to end flat against the horizontal meridian (Fig. 39-3C). This type of field defect mirrors the arrangement of the nerve fiber layer in the temporal retina. Arcuate or nerve fiber layer scotomas also result from optic neuritis, ischemic optic neuropathy, optic disc drusen, and branch retinal artery or vein occlusion. Damage to the entire upper or lower pole of the optic disc causes an altitudinal field cut that follows the horizontal meridian (Fig. 39-3D). This pattern of visual field loss is typical of ischemic optic neuropathy but also results from retinal vascular occlusion, advanced glaucoma, and optic neuritis.

Central retinal artery occlusion

Central retinal artery occlusion (CRAO) is a disease of the eye where the flow of blood through the central retinal artery is blocked (occluded). There are several different causes of this occlusion; the most common is carotid artery atherosclerosis. Signs and symptoms Central retinal artery occlusion is characterized by painless, acute vision loss in one eye. Upon fundoscopic exam, one would expect to find: cherry-red spot (90%) (a morphologic description in which the normally red background of the choroid is sharply outlined by the swollen opaque retina in the central retina), retinal opacity in the posterior pole (58%), pallor (39%), retinal arterial attenuation (32%), and optic disk edema (22%). During later stages of onset, one may also find plaques, emboli, and optic atrophy. Diagnosis

Maculopathy

A maculopathy is any pathological condition of the macula, an area at the centre of the retina that is associated with highly sensitive, accurate vision. Forms of maculopathies Age-Related Macular Degeneration is a degenerative maculopathy associated with progressive sight loss. It is characterised by changes in pigmentation in the Retinal Pigment Epithelium, the appearance of drusen on the retina of the eye and choroidal neovascularization. AMD has two forms; 'dry' or atrophic/non-exudative AMD, and 'wet' or exudative/neovascular AMD. Malattia Leventinese (or Doyne’s honeycomb retinal dystrophy) is another maculopathy with a similar pathology to wet AMD. Cellophane Maculopathy A fine glistening membrane forms over the macula, obscuring the vision.

Long-term follow-up of a case of Coats disease in a 10-year-old boy with spontaneous peeling of preretinal macular fibrosis: a case report.

Coats disease is a retinal vascular disorder characterized by aneurysms and telangiectasias. Macular fibrosis is a complication of Coats disease that results in vision loss. Macular fibrosis rarely develops in the natural course and often occurs after treatment with intravitreal bevacizumab, photocoagulation, or cryotherapy. Here, we have described an unusual case of spontaneous peeling of preretinal macular fibrosis in a patient with untreated Coats disease. A 10-year-old Japanese boy presented with vision loss in his left eye. The patient's left visual acuity was 20/28. Fundus examination of his left eye revealed thick preretinal macular fibrosis around the optic disc and macula. In addition, retinal telangiectasis, microaneurysms, hard exudates, and retinal hemorrhages were observed in the left peripheral temporal retina. We diagnosed his condition as Coats disease with preretinal macular fibrosis. Two months later, optical coherence tomography revealed preretinal macular fibrosis detachment at the foveal lesion without any treatment. During follow-up, preretinal macular fibrosis at the macular lesion was completely detached. Further, posterior vitreous detachment was observed and the shape of the macula and the patient's left visual acuity had improved. In our case, both formation and spontaneous peeling of preretinal macular fibrosis occurred without any treatment for Coats disease, which is an unusual finding. Vitreous changes might have occurred during the natural clinical course, causing subsequent posterior vitreous detachment and resulting in spontaneous peeling of fibrosis.

A Case of Idiopathic Dense Vitreous Hemorrhage: Suspected Rupture of a Large Retinal Arterial Macroaneurysm on the Optic Disc.

We report a novel case of vitreous hemorrhage associated with suspected rupture of 2-disc-diameter retinal arterial macroaneurysm on the optic disc. A 90-year-old woman presented with blurred vision (sudden onset) in her left eye. Examination of the fundus revealed acute onset vitreous hemorrhage of unknown origin without retinal detachment. She underwent vitrectomy, but after excision of the dense vitreous hemorrhage, a 2-disc-diameter hematoma appeared on the optic disc and was removed promptly. Because the bleeding at the base of the hematoma was of arterial origin and pulsating, the first vitrectomy could not achieve hemostasis. Five days after the first surgery, we performed a second vitrectomy. This revealed a subretinal hemorrhage along the superior and inferior arcade vessels and a macular hole, which was almost completely closed with an inverted internal limiting membrane flap. Unfortunately, the macular hole reopened 41 days after the second surgery. In patients presenting with only a large hematoma on the optic disc, it might be prudent to leave the hematoma. However, this large retinal arterial macroaneurysm was on a rare location on the optic disc, making it doubly difficult for the surgeons to diagnose and choose the best option intraoperatively. The differential diagnosis for dense vitreous hemorrhage of unknown origin should include a large retinal arterial macroaneurysm on the optic disc.

Clinical Features and Course of Patients with Peripheral Exudative Hemorrhagic Chorioretinopathy.

To evaluate the clinical characteristics of patients who were followed in our clinic with the diagnosis of peripheral exudative hemorrhagic chorioretinopathy (PEHC). Medical records of 12 patients who were diagnosed with PEHC in İstanbul University İstanbul Faculty of Medicine, Department of Ophthalmology between July 2006 and June 2014 were reviewed retrospectively. This study included 21 eyes of 12 patients. Four (33.3%) of the patients were male and 8 (66.7%) were female and ages ranged between 73 and 89 years. Eight (66.7%) of the patients were referred to us with the diagnosis of choroidal mass. Unilateral involvement was found in 3 and bilateral involvement in 9 patients. Temporal quadrants were involved in all eyes. Fifteen eyes (71.4%) had subretinal hemorrhage and hemorrhagic/serous retinal pigment epithelial detachment, 11 (52.4%) had lipid exudation, 5 (23.8%) had chronic retinal pigment epithelium alterations, 2 (9.5%) had subretinal fibrosis and 1 (4.8%) had vitreous hemorrhage. PEHC lesions were accompanied by drusen in 11 eyes (52.4%), geographic atrophy in 2 eyes (9.5%), and choroidal neovascularization scar in 2 eyes (9.5%). Treatment was done in both eyes of a patient for lesions which threatened the macula, in a patient with bilateral macular edema and in a patient with vitreous hemorrhage. The remaining eyes were followed-up without any treatment because the lesions did not threaten the macula and they showed no progression during follow-up. PEHC is a degenerative disease of peripheral retina that is seen in older patients, and signs of age-related macular degeneration (AMD) may accompany this pathology. Especially in patients with AMD findings, the peripheral retina must be evaluated carefully for existing PEHC lesions.

[Clinical picture of isolated retinal vasculitis].

Clinical picture of isolated retinal vasculitis (IRV) in 43 patients (25 men and 18 women) aged 22-42 years is analyzed. IRV was bilateral in 88.4% cases and involved the veins. Two forms of disease were distinguished: peripheral (in 75%) and central-peripheral (25%). Both forms were characterized by a high hemorrhagic activity, occlusion of vessels, ischemic zones and neovascularization of the retina and optic disk, but these signs were more frequent in central peripheral form of IRV. IRV is a grave disease leading to poor vision or blindness in 18% cases. The onset is poorly manifest with floating spots and blurred vision; the main symptom is vitreous hemorrhage. Visual acuity was significantly decreased in patients with occlusive IRV in comparison with those without occlusions (0.32 +/- 0.37 vs. 0.77 +/- 0.28). The earliest changes can be detected mainly in the peripheral parts of the retina. This necessitates special attention of ophthalmologist to seemingly negligible complaints of patients and thorough examination of the fundus oculi, particularly of its peripheral sections, which can be performed only on condition of adequate mydriasis. Only timely diagnosis and early pathogenetic therapy can decrease the probability of such complications as hemophthalmos, retinal neovascularization, detachment of retina, and neovascular glaucoma, and prevent disability.

Metamorphopsia

Pathology The mechanisms that result in the development of metamorphopsia involve structural changes in the retina of the eye (retinal mechanism) as well as processing changes in the cerebral cortex of the brain (cortical mechanism). The retinal mechanism involves the displacement of retinal layers which results in the mislocation of light on the retina. The cortical mechanism, which was discovered after the retinal mechanism, is affected by perceptual “filling-in” and visual crowding effects. The cortical mechanism was found to work in combination with the retinal mechanism to contribute to metamorphopsia in long-standing maculopathy or after the treatment of macular disorders. Causes of Metamorphopsia Metamorphopsia can be a symptom of a number of eye disorders involving the retina or macula. Some of these conditions include the following: Age-related macular degeneration Epiretinal membrane and vitreomacular traction Posterior vitreous detachment Macular hole

[Three cases of retinal arterial macroaneurysm on the optic disc].

Retinal arterial macroaneurysm typically involves the second order arterioles and is relatively uncommon on the optic disc. Here, we present three cases of retinal arterial macroaneurysm. Case 1 was a 56-year-old woman, Case 2 was a 78-year-old man, and Case 3 was an 86-year-old man. In Cases 1 and 3, the fundus could not be observed visually at the time of initial examination because of vitreous bleeding. Retinal arterial macroaneurysm was revealed during vitrectomy. In Case 2, retinal arterial macroaneurysm was found on the optical disc along with a retinal hemorrhage which disappeared without any treatment. In all three cases, visual acuity was normal after treatment. Since retinal arterial macroaneurysm on the optical disc may be overlooked when treating vitreous bleeding in cases where the cause is not known, we believe that retinal arterial macroaneurysm should be taken into consideration as a possible underlying cause. While photocoagulation of retinal arterial macroaneurysm on the optic disc is infrequently used to, localized photocoagulation retinal arterial macroaneurysm on the optic disk is considered to be difficult. We are of the opinion that progression should be observed carefully till the macroaneurysm is absorbed.

InternalMed_Harrison

Anterior Ischemic Optic Neuropathy (AION) This is caused by insufficient blood flow through the posterior ciliary arteries that supply the optic disc. It produces painless monocular visual loss that is sudden in onset, followed sometimes by stuttering progression. The optic disc appears swollen and surrounded by nerve fiber layer splinter hemorrhages (Fig. 39-9). AION is divided into two forms: arteritic and nonarteritic. The nonarteritic form is most common. No specific cause can be identified, although diabetes and hypertension are common risk factors. A crowded disc architecture and small optic cup predispose to the development of nonarteritic AION. No treatment is available. About 5% of patients, especially those age >60, develop the arteritic form of AION in conjunction with giant-cell (temporal) arteritis (Chap. 385). It is urgent to recognize arteritic AION so that high doses of glucocorticoids can be instituted immediately to prevent blindness in the second eye. Symptoms of

Severe vision loss secondary to retinal arteriolar occlusions after multiple intravitreal brolucizumab administrations.

To describe a case of unilateral retinal arteriolar occlusion following multiple intravitreal brolucizumab injections for neovascular age-related macular degeneration (nAMD). A 92-year-old Caucasian woman presented with blurry vision in her left eye (OS) after receiving the third dose of intravitreal brolucizumab. At the time of presentation, visual acuity (VA) was 20/40 in her right eye (OD) and had decreased from 20/150 to count finger (CF) at 1-foot OS. On examination, there was no evidence of active inflammation in the anterior chamber OU. Dilated fundus examination showed no vitritis in OD and 1+ vitreous cells OS, flame-shaped hemorrhage at the superior optic disc margin, and retinal whitening surrounding the proximal portion of the supero-temporal branch of the central retinal artery. There were drusen in OS and retinal pigment epithelial (RPE) changes in the maculae of OU. Intra-arteriolar greyish deposits were seen OS. Fluorescein angiography (FA) showed hyper-fluorescence in the maculae corresponding to fibrovascular pigment epithelial detachments (PED) OU. No peri-vascular leakage was noted OU. Delayed filling of multiple arterioles in early and late phases OS was observed on FA. The patient was diagnosed with retinal arteriolar occlusion associated with repeated intravitreal brolucizumab administrations. Retinal arteriolar occlusion with severe vision loss, possibly secondary to inflammatory responses, can occur after subsequent intravitreal brolucizumab injections, even if no inflammation occurred after initial administrations. Vaso-occlusive disease should be considered as a potential ocular complication, with acute as well as delayed onset, following intravitreal brolucizumab therapy.

[Hemorrhagic complications in drusen of the optic papilla].

A case of optic disc drusen complicated by retinal hemorrhages similar to those seen in central retinal vein occlusion is presented. While haemorrhagic complications of optic disc drusen are rare, three types have been described: small disk haemorrhages, vitreous haemorrhages and deep peripapillary haemorrhages. This clinical aspect of the haemorrhagic retinopathy presented in this paper has rarely been described; the pathogenesis of this lesion can be attributed to a progressive compression by the drusen on the central vein in the optic disk, causing a venous stasis retinopathy. Since it is impossible to remove the cause of the venous compression, the prognosis of this clinical form is always poor. Finally, the author emphasizes the need to consider this rare complication of drusen of the optic disk, especially in young patients with no systemic pathology who present this ophthalmoscopic picture, in order to avoid useless, time consuming tests and ineffective therapies.

Macular degeneration

AMD-like pathology begins with small yellow deposits (drusen) in the macula, between the retinal pigment epithelium and the underlying choroid. Most people with these early changes (referred to as age-related maculopathy) still have good vision. People with drusen may or may not develop AMD. In fact, the majority of people over age 60 have drusen with no adverse effects. The risk of developing symptoms is higher when the drusen are large and numerous, and associated with the disturbance in the pigmented cell layer under the macula. Large and soft drusen are thought to be related to elevated cholesterol deposits. Early AMD Early AMD is diagnosed based on the presence of medium-sized drusen, about the width of an average human hair. Early AMD is usually asymptomatic. Intermediate AMD Intermediate AMD is diagnosed by large drusen and/or any retinal pigment abnormalities. Intermediate AMD may cause some vision loss, but, like early AMD, it is usually asymptomatic.

[Acute posterior multifocal epitheliopathy: case report].

To present an atypical course of acute posterior multifocal placoid epitheliopathy. 59 years-old diabetic man was seen at emergency because of a few days history of blurred vision in his right eye. Ophthalmologic examination revealed patches of blurred margine, multiple, yellowish lesions 1-2 dd in the fundus in both eyes. There were also lesions typical for non proliferative diabetic retinopathy like microaneurysms, dot and blot intraretinal hemorrhages and hard exudates. Optic discs and blood vessels were normal. We found peripheral drusen extending from the equator to the ora serata in both eyes. During 8 months of observation, we performed three times ophthalmologic examination, fluorescein and indocyanine green angiographies, USG A and B. No treatment was given. There is disagreement about the site of origin of placoid lesions, etiology and pathogenesis in acute posterior multifocal placoid epitheliopathy. In our report we agree with thesis, that the choriocapillaris are the primary site of the break. We propose, that different duration of the APMPPE and recurrences are directly proportional to the state and quality of the blood vessels. The possible explanation for longstanding lesions in our patient is diabetic damage of the capillaries in the retina and choroid.

[Characteristics of optical coherence tomography for exudative age-related macular degeneration].

To observe the characteristics of optical coherence tomography (OCT) for exudative age-related macular degeneration (AMD). Thirty-eight patients (42 eyes) diagnosed as exudative AMD by color fundus photography, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were examined by OCT. The results of OCT were analyzed and compared with that of FFA and ICGA. The characteristics of OCT for exudative AMD: fibrotic choroidal neovascularization (34 eyes), serous detachment of neurosensory epithelium (38 eyes), detachment of the nerve fiber layer (8 eyes), and hemorrhagic and serous detachment of retinal pigment epithelium (11 eyes and 9 eyes, respectively). The major characteristic of OCT of exudative AMD is fibrotic choroidal neovascularization combined with serous and hemorrhagic detachment of neurosensory epithelium or retinal pigment epithelium, which would be helpful for diagnosing and evaluating exudative AMD.

[Ophthalmological manifestations of arterial hypertension].

Systemic Arterial hypertension (AHT) is one of the most frequent diseases in the industrialised countries, with an incidence reaching 30%, a figure that is rising due to the greater life expectancy of the population. This rise in arterial tension causes, or accelerates, changes in the vascular wall of the target organs such as the kidney, brain, heart and eye. At the ocular level, AHT produces lesions in the retina, the choroids and optic nerve head; this can include a wide range of lesions, from slight vascular narrowing to severe visual loss due to ischaemic optical neuropathy. The primary response of the retinal arteries to systemic arterial hypertension is vascular narrowing and the manifestations that appear at the back of the eye in hypertensive retinopathy are diffuse or focal vasoconstriction, extravasation due to increased vascular permeability and arteriosclerosis with swelling of the wall of the vessels. These three entities are responsible for the appearance of different lesions that characterise the stages of the retinal disease, which are: arteriovenous crossings, hard and cotton-like exudates, thrombosis, embolisms, haemorrhages in the retinal parenchyma, vitreous detachment from the retina, papilla edema and ischaemic optical neuropathy in the more severe cases, such as in case malign arterial hypertension.

Multimodal imaging findings in a case of severe Central Serous Chorioretinopathy in an uncomplicated pregnancy.

Central Serous Chorioretinopathy (CSC) has been previously reported as an infrequent complication of pregnancy that usually resolves spontaneously after delivery, with minimal or no sequel. We report a case of a severe form of CSC in an uncomplicated pregnancy with extensive subfoveal exudates and severe permanent visual loss. Multimodal imaging techniques, including color and red-free photographs, near-infrared reflectance, fluorescein angiography, and spectral-domain optical coherence tomography, were performed and the findings were correlated to the changes in visual acuity. A 35-year-old pregnant woman presented with loss of vision and metamorphopsia in her left eye. Fundus examination showed subfoveal severe exudation with a posterior pole serous detachment. Optical coherence tomography (OCT) showed macular neurosensory detachment with central highly reflective sub-retinal material. Multimodal fundus pictures and angiograms revealed distinct clinical features of the disease during both the acute and final phase. The disease spontaneously resolved after delivery with regression of the subretinal fluid and the disappearance of subfoveal exudates. Nevertheless, because of severe atrophic macular changes and subfoveal fibrosis, no improvement of visual acuity was noted. Severe variants of CSC may also present in cases of uncomplicated pregnancy and result in a poor prognosis. Recognising these presentations of CSC is critical to avoid improper management. Multimodal imaging may help to clarify the diagnosis and highlight the clinical features.

InternalMed_Harrison

Retinal arterial occlusion also occurs rarely in association with retinal migraine, lupus erythematosus, anticardiolipin antibodies, anticoagulant deficiency states (protein S, protein C, and antithrombin deficiency), pregnancy, IV drug abuse, blood dyscrasias, dysproteinemias, and temporal arteritis. Marked systemic hypertension causes sclerosis of retinal arterioles, splinter hemorrhages, focal infarcts of the nerve fiber layer (cottonwool spots), and leakage of lipid and fluid (hard exudate) into the macula (Fig. 39-7). In hypertensive crisis, sudden visual loss can result from vasospasm of retinal arterioles and retinal ischemia. In addition, acute hypertension may produce visual loss from ischemic swelling of the optic disc. Patients with acute hypertensive retinopathy should be treated by lowering the blood pressure. However, the blood pressure should not be reduced precipitously, because there is a danger of optic disc infarction from sudden hypoperfusion.

Posterior vitreomacular adhesion: a potential risk factor for exudative age-related macular degeneration?

To compare the state of the posterior vitreous in exudative age-related macular degeneration (AMD) with eyes with nonexudative AMD and controls. Prospective, observational case series. B-scan ultrasonography and optical coherence tomography (OCT) were performed in 163 eyes from 82 subjects older than 55 years, 50 eyes with exudative AMD, 57 with nonexudative AMD, and 56 control eyes. Main outcome measures were the number of eyes with complete posterior vitreous detachment (PVD) by ultrasound and the number of eyes with central vitreomacular adhesion by OCT. By ultrasonography, 17 (34.0%) of 50 eyes with exudative AMD had PVD as compared with 41 (71.9%) of 57 eyes with nonexudative AMD (P = .00002) and 34 (60.7%) of 56 controls (P = .017). OCT detected persistent central vitreoretinal adhesion surrounded by a detached posterior vitreous cortex in 18 (36%) of 50 eyes with exudative AMD, significantly higher than in nonexudative AMD (4/57 [7%]; P < .0001) and in controls (6/56 [10%]; P = .002). Persistent attachment of the posterior vitreous cortex to the macula may be another risk factor for the development of exudative AMD via vitreoretinal traction inducing chronic low-grade inflammation, by maintaining macular exposure to cytokines or free radicals in the vitreous gel, or by interfering in transvitreous oxygenation and nutrition of the macula. Inducing PVD may provide prophylactic benefit against exudative AMD.

InternalMed_Harrison

• Next, examine the macula. The macula is the area between the superior and inferior temporal vascular arcades, and its center is the fovea. You can examine the macula by pointing your ophthalmoscope about 15° temporal to the optic disc. Alternatively, ask the patient to look into the center of the light. Note the foveal reflex and the presence of any hemorrhage, exudate, abnormal blood vessels, scars, deposits, or other abnormalities. • Examine the retinal blood vessels by re-identifying the optic disc and following each of the four main branches away from the disc. The veins are dark red and relatively large. The arteries are narrower and bright red. • Ask the patient to look in the eight cardinal directions to allow you to view the peripheral fundus. In a patient with a well-dilated pupil, it is possible to visualize as far as the equator.