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Classification of hypertensive fundus changes and their order of appearance.

We studied the sequence of appearance of the various fundus lesions in experimentally produced renovascular malignant arterial hypertension in 60 rhesus monkeys. The earliest lesion to appear usually was focal intraretinal periarteriolar transudates (FIPTs). Some time after that, three lesions: acute focal retinal pigment epithelial lesions, macular edema and optic disk edema, developed at roughly the same time. Cotton-wool spots appeared after these lesions. Retinal lipid deposits developed relatively late. Retinal arteriolar changes were a much later phenomenon. Conspicuous retinal hemorrhages were not a common or prominent early sign. The various classifications of hypertensive fundus changes proposed in the literature are reviewed and discussed critically, and it is concluded that, instead of using the various arbitrary grades advocated in different classifications, it is more informative and clinically useful to give a descriptive account of the individual fundus lesions revealed by ophthalmoscopy and fluorescein fundus angiography; because different lesions have different degrees of significance.

Animals↗

Posterior segment complications in patients with hepatitis C treated with interferon and ribavirin.

PURPOSE: To determine the incidence and type of posterior segment complications associated with the use of interferon alpha 2b and ribavirin in patients with chronic hepatitis C. DESIGN: A prospective noncomparative case series. PARTICIPANTS: Forty-two patients (84 eyes). METHODS: Patients with chronic hepatitis C were evaluated for ocular changes while being treated with interferon alpha 2b and ribavirin. Patients were followed with sequential ocular examinations for 4 to 20 months. MAIN OUTCOME MEASURES: Occurrence of posterior segment complications while on interferon and ribavirin therapy. RESULTS: Twenty-seven patients developed retinopathy. The retinopathy consisted of single-to-multiple cotton-wool spots and retinal hemorrhage and was transient in all cases. An additional patient (age 46) presented with asymptomatic disc edema and hemorrhage. One other individual developed a symptomatic permanent monocular visual field defect. Therapy was discontinued in three patients because of severe posterior segment pathology. CONCLUSIONS: Our study demonstrated that a high incidence of retinopathy is associated with the treatment of hepatitis C using interferon and ribavirin, but that this form of retinopathy is relatively benign. Regular ophthalmic monitoring should be performed in patients undergoing this treatment.

Adult↗

[The ocular ischemic syndrome].

The ocular ischemic syndrome is caused by severely reduced ocular perfusion, usually secondary to carotid artery stenosis. Because of the low perfusion pressure, anterior chamber rubeosis does not invariably lead to increased intraocular pressure. The characteristic ocular pain is unrelated to the intraocular pressure. Patients adapt slowly to increasing light intensity (bright light amaurosis fugax). Retinal hemorrhages often lead to the mistaken assumption that the patient has diabetic retinopathy, especially when the patient has diabetes. A definite diagnosis is made by the demonstration of severely decreased ocular perfusion pressure. Supporting evidence is delayed filling on fundus fluorescein angiography in a patient with high-grade carotid artery stenosis. The majority of affected eyes lose vision for finger counting within one year. No treatment of documented value is available. Patients without neovascularization of the anterior chamber angle may occasionally experience improved vision after carotid surgery.

Carotid Stenosis↗

Fine-needle aspiration biopsy of suspected intraocular tumors. The 1992 Urwick Lecture.

BACKGROUND: Fine-needle aspiration biopsy recently has been used as a diagnostic modality for selected intraocular tumors and simulating conditions. However, the value of fine-needle aspiration biopsy for intraocular tumors previously has not been clarified. METHODS: Transocular fine-needle aspiration biopsy was performed on selected patients who had intraocular lesions that were suspected clinically to be neoplasms but in which there was diagnostic uncertainty based on noninvasive clinical evaluation. These cases were analyzed to determine accuracy, complications, and limitations of the technique. RESULTS: Of 6500 patients referred to the Oncology Service for evaluation of possible intraocular tumor, transocular fine-needle aspiration biopsy was used clinically in 159 cases (2.4%). It proved to be a reliable diagnostic method for intraocular malignancies such as uveal melanoma, uveal metastasis, retinoblastoma, lymphoma, and leukemia. In the 140 cases (88%) in which adequate cytologic material was obtained, the sensitivity rate was 100% and the specificity rate was 98%. In 19 cases where the cytologic material was too scant to render a diagnosis, the sensitivity rate was 84% and the specificity rate was 98%. The problem of insufficient material for cytologic diagnosis has been greatly minimized with the recent use of a 22-gauge needle. The main complication was localized intraocular hemorrhage. Retinal detachment and tumor recurrence have not been observed. CONCLUSIONS: Transocular fine-needle aspiration biopsy is a safe and reliable diagnostic method for suspected intraocular tumors and inflammatory conditions in which noninvasive diagnostic modalities have failed to establish the diagnosis and in which cytologic verification of the diagnosis is necessary to institute appropriate treatment. Although the authors have had few complications with fine-needle aspiration biopsy, the technique should be reserved for selected cases where the diagnosis has not been established by less-invasive diagnostic measures.

Anterior Eye Segment↗

[Idiopathic polypoidal choroidal vasculopathy leading to blindness].

Idiopathic polypoidal choroidal vasculopathy (IPCV) has recently been recognized as a distinct cause of recurrent subretinal hemorrhages and exudates as well as multiple hemorrhagic retinal pigment epithelium detachments in the macula. IPCV is usually considered to have a good visual prognosis. We report the case of a 44-year-old woman with particularly severe bilateral macular and peripheral IPCV. The patient was followed for 13 years and had final visual acuity of counting fingers in the right eye and 20/400 in the left eye. Patients with IPCV with macular choroidal neovascularization tend to have a poor visual prognosis. This case of IPCV should alert the physician to be particularly attentive to the follow-up of these patients.

Blindness↗

[Warfarin potassium for impending central retinal vein occlusion].

PURPOSE: We reviewed the records of 10 patients who had impending central retinal vein occlusion in order judge whether anticoagulant treatment with warfarin potassium (Warfarin) was indicated. PATIENTS: 6 men and 4 women, ranging in age from 25 to 83 (average 55) years were studied. RESULTS: Of 6 eyes, retinal hemorrhage disappeared completely within 6 months. Four patients whose visual acuity was 0.1 or less at one month needed photocoagulation. Four other patients whose late venous circulation time at fluorescein angiography improved within 30 seconds had good visual prognosis, 3 eyes of 4 patients aged 65 or older were not successful in regaining their visual acuity. CONCLUSION: Warfarin was not effective for patients who had clearly lost their visual acuity and the elderly in this series. Late venous circulation time at fluorescein angiography was a useful index for this treatment.

Adult↗

[Macular serous detachment revealing acute lymphoblastic leukemia].

BACKGROUND: Leukemias are a group of malignant diseases caused by immature hematopoietic cells proliferating in the blood marrow. Some manifestations result from ocular-orbital involvement, which usually occurs through the central nervous system. Other manifestations stem from vasculopathy and/or hemorheologic disorders (anemia, thrombocytopenia, hyperviscosity). OBSERVATION: We report a case of a 42-year-old women presenting with loss of vision caused by serous macular detachment. The investigations showed the diagnosis of acute lymphoblastic leukemia. Steroids and chemotherapy led to complete remission with normal visual acuity during a follow-up of 29 months. DISCUSSION: Ocular involvement is seen in 28%-80% of leukemia cases. The most obvious findings are the presence of retinal hemorrhages, which are most commonly located in the posterior pole. The intraretinal hemorrhage may contain a white component that usually is a white dot in the center of the hemorrhage, but other clinical features are described. Serous detachment of the neuroepithelium is seldom reported, and can be the first symptom of the disease. Other ocular findings include infiltrative involvement of the chorioretina, anterior segment involvement, and orbital location. Ocular location is estimated to be an equivalent of central nervous system involvement, and subsequently requires adequate treatment (steroids, chemotherapy and radiotherapy of the central nervous system). CONCLUSION: Ocular manifestations of leukemia are frequent but rarely reveal the disease. Serous detachment is rarer. However, the diagnosis of leukemia should be considered in case of pigmentary epithelium involvement.

Adult↗

Retinal microvascular abnormalities and cognitive impairment in middle-aged persons: the Atherosclerosis Risk in Communities Study.

BACKGROUND AND PURPOSE: Cerebral microvascular disease has been hypothesized to contribute to cognitive impairment, but few clinical data are available. Here, we examine the relation of retinal microvascular abnormalities with cognitive function in middle-aged persons free of stroke. METHODS: The Atherosclerosis Risk in Communities Study is a population-based study with examinations every 3 years from 1987 through 1998. At visit 3, when participants were 51 to 70 years of age, retinal photographs were obtained and evaluated for retinal microvascular abnormalities according to standardized protocols. Cognitive function was assessed with standardized tests (Delayed Word Recall Test, Digit Symbol Subtest, and Word Fluency Test) at visits 2 and 4 and averaged for analysis. Persons with stroke or taking central nervous system-relevant medications were excluded, leaving 8734 with data for this study. RESULTS: After education, diabetes mellitus, blood pressure, carotid intima-media thickness, and other risk factors were controlled for, retinopathy was associated with lower cognitive test scores. The adjusted odds ratios for persons with Delayed Word Recall scores 2 SD or lower than the mean were 2.60 [95% confidence interval (CI), 1.30 to 2.91] for any retinopathy, 3.00 (95% CI, 1.81 to 4.98) for microaneurysms, 3.39 (95% CI, 1.99 to 5.78) for retinal hemorrhage, and 3.07 (95% CI, 1.53 to 6.17) for soft exudates. Results were similar for the other 2 cognitive tests and in people with and without diabetes and hypertension. CONCLUSIONS: Retinopathy is independently associated with poorer cognitive function in middle-aged persons without stroke, suggesting that cerebral microvascular disease may contribute to the development of cognitive impairment.

Aged↗

Retinopathy associated with high-dose interferon alfa-2b therapy.

PURPOSE: To present seven patients who developed retinopathy while receiving high-dose interferon alfa-2b therapy for adjuvant treatment of high-risk melanoma. METHODS: Retrospective case series. RESULTS: Seven patients developed a retinopathy while receiving high-dose interferon alfa-2b therapy for adjuvant treatment of high-risk melanoma. Five patients had normal visual acuity, but retinopathy with cotton- wool spots and/or retinal hemorrhages with the retinopathy resolved after stopping treatment after detection. Two patients developed severe retinopathy with vision loss to counting fingers and hand motions without resolution of the retinopathy. The duration of the maintenance treatment before detection of the retinopathy for all patients ranged from 6 to 26 weeks. The total dose received at time of detection of retinopathy ranged from 816 to 1770 million units. Confounding factors included hypertension, thrombocytopenia, anemia, and a history of prior chemotherapy in one patient. Also, one patient received an investigational ganglioside vaccine, one had a history of radiation treatment to the brain, and six received paroxetine. CONCLUSIONS: Patients receiving interferon alfa-2b are at risk for developing an associated retinopathy. The risk appears to be greater with higher dosage therapy. In addition, severe vision loss can be seen with interferon alfa-2b-associated retinopathy. The effect of treatment with selective serotonin reuptake inhibitors, such as paroxetine, in increasing the incidence of this complication is unknown. Patients need to be monitored until the retinopathy is resolved to screen for sequelae, including retinal neovascularization.

Dose-Response Relationship, Drug↗

Microvasculopathy in the ocular fundus after bone marrow transplantation.

OBJECTIVE: To determine the incidence and time course of retinal and optic-disk ischemia after bone marrow transplantation and to describe the clinical, fluorescein-angiographic, and histologic findings in patients with these ischemic fundus lesions. DESIGN: Prospective cohort study; standardized clinical and ophthalmologic evaluation of all patients before bone marrow transplantation and 3, 6, and 12 months after transplantation (and when indicated). SETTING: University hospitals in Basel, Switzerland. PATIENTS: Consecutive patients (127) treated with allogeneic or autologous bone marrow grafts. MAIN RESULTS: Thirteen of the 127 patients (10%; 95% Cl, 5% to 15%) had lesions of the ocular microcirculation. All patients had cotton-wool spots in the fundus of both eyes, and three patients also had bilateral optic-disk edema. Secondary changes included retinal hemorrhages and lipid deposits. The ischemic fundus lesions appeared during the first 6 months after transplantation and were reversible in 9 of the 13 patients. The lesions occurred only in patients who were treated with total body irradiation and were given cyclosporin A as prophylaxis for graft-versus-host disease. CONCLUSIONS: Ischemic fundus lesions are a frequent complication after bone marrow transplantation. They were only observed in patients treated with total body irradiation and cyclosporin A. This combination of therapy appears to have an additive effect on the development of ocular and possibly generalized microvascular lesions.

Adolescent↗

A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion. The Central Vein Occlusion Study Group N report.

PURPOSE: To answer whether prophylactic panretinal photocoagulation (PRP) in ischemic central vein occlusion (CVO) prevents development of 2 clock hours of iris neovascularization or any angle neovascularization (TC-INV/ANV) or whether it is more appropriate to apply PRP only when TC-INV/ANV occurs. METHODS: Multicenter randomized controlled clinical trial in eyes with ischemic CVO. Eyes were assigned to immediate prophylactic PRP (90 eyes) or to frequent close observation (91 eyes). If TC-INV/ANV developed, untreated eyes received PRP and previously treated eyes received supplemental PRP. RESULTS: In both groups, TC-INV/ANV developed less often in prophylactically treated than untreated eyes, but the difference was not statistically significant when adjusted for baseline imbalance. Treatment of TC-INV/ANV was followed by prompt regression (within 1 month) in 18 (56%) of 32 previously untreated eyes and in 4 (22%) of 18 eyes that had had prophylactic treatment. All eyes except eight eventually stabilized without neovascularization. TC-INV/ANV was correlated with the amount of nonperfused retina (P = 0.0001) and extent of retinal hemorrhage (P = 0.03). Males were at higher risk than females for TC-INV/ANV (P = 0.01), as were patients with occlusions of less than one month duration (P = 0.01). CONCLUSIONS: Prophylactic PRP does not totally prevent TC-INV/ANV, and prompt regression of TC-INV/ANV in response to PRP is more likely to occur in eyes that have not been treated previously. The authors recommend careful observation with frequent follow-up examinations in the early months (including undilated slit-lamp examination of the iris and gonioscopy) and prompt PRP of eyes in which TC-INV/ANV develops.

Adult↗

Natural history and clinical management of central retinal vein occlusion. The Central Vein Occlusion Study Group.

OBJECTIVE: To provide clinical management guidelines for eyes with central retinal vein occlusion. DESIGN: Prospective cohort study with randomized clinical trials of specific subgroups of patients. Three-year follow-up every 4 months. SETTING: Nine ophthalmology practices. PATIENTS: Seven hundred twenty-five patients with central vein occlusion. MAIN OUTCOME MEASURES: Iris neovascularization (INV), neovascular glaucoma, and visual acuity. RESULTS: Visual acuity outcome was largely dependent on initial acuity. Sixty-five percent of patients with initially good visual acuity (20/40 or better) maintained visual acuity in the same range at the end of the study. Patients with intermediate initial acuity (20/50-20/200) showed a variable outcome: 19% improved to better than 20/50, 44% stayed in the intermediate group, and 37% had final visual acuity worse than 20/200. Patients who had poor visual acuity at the first visit (< 20/200) had an 80% chance of having a visual acuity less than 20/200 at final visit, whether perfused or nonperfused initially. In the first 4 months of follow-up, 81 (15%) of the 547 eyes with perfusion converted to ischemia. During the next 32 months of follow-up, an additional 19% of eyes were found to have converted to ischemia for a total of 34% after 3 years. The development of nonperfusion or ischemia was most rapid in the first 4 months and progressed continuously throughout the entire duration of follow-up. Iris neovascularization of at least 2-clock hours, and/or angle neovascularization (ANV) developed in 117 (16%) of the 714 eyes. Sixty-one of the 117 eyes that had INV/ANV were initially categorized as nonperfused or indeterminate; 56 of the 117 eyes were initially categorized as perfused. When INV/ANV occurred, it was treated promptly with panretinal photocoagulation. The strongest predictors of INV/ANV were visual acuity (P < .001) and the amount of nonperfusion seen by fluorescein angiogram (P < .001). For eyes initially categorized as nonperfused or indeterminate, 35% (61/176) developed INV/ANV, compared with 10% (56/538) for eyes initially categorized as perfused. Other risk factors were venous tortuosity (P = .02), extensive retinal hemorrhage (P = .07), and duration less than 1 month (P = .08). Neovascular glaucoma that was unsuccessfully managed with medical treatment developed in only 10 eyes. No eye was enucleated. CONCLUSIONS: Visual acuity at baseline is a strong predictor of visual acuity at 3 years for eyes with good vision and eyes with poor vision, but a poor predictor for intermediate acuities. Visual acuity is also a strong predictor for the development of INV/ANV, as is nonperfusion. During the course of follow-up, one third of the eyes with perfusion converted to eyes with ischemia. Clinical management guidelines, developed from these and previously reported Central Vein Occlusion Study data, are presented.

Aged↗

The natural history of the first clinically visible features of diabetic retinopathy.

Microaneurysms are the first features of human diabetic retinopathy that can be detected with common clinical techniques. These are found, most often, in photographic field 2 (that is, an area occupying 30 degrees of the ocular fundus centered on the middle of the macula). After the first microaneurysms develop, there will be a tendency for more to appear; however, over time many of the original microaneurysms will become no longer visible with clinical techniques, while other, newer, microaneurysms mature. After the onset of microaneurysms, several years may pass before any other diabetic retinopathic lesions develop. Lesions other than microaneurysms were uncommon in this study; the following is a list in decreasing frequency: retinal hemorrhages, soft exudates, IRMA, hard exudates, and venous beading. During the 4 years of this study, there were no other diabetic retinopathic lesions detected. The duration of insulin-dependent diabetes mellitus was related to the rate of change in microaneurysm counts. The age and sex of patients did not affect this rate of change. The accuracy of metabolic control, as determined by glycosylated hemoglobin levels, may influence this rate of change; however, this was detected only at the extremes of measurement in this study. The equipment available to most ophthalmologists can detect the earliest clinical aspects of diabetic retinopathy. These features can be quantified in a reproducible manner with standardized photographic techniques to permit satisfactory data analysis.

Adolescent↗

Management of sickle cell disease: progress during the past 10 years.

Despite the lack of successful drug development during the last 10 years, significant advances have been made in the management of a number of the complications of sickle cell disease. Identification of the vascular changes in the retina has led to the use of argon or zenon laser therapy to prevent progression of these changes to retinal hemorrhage and loss of visual acuity. Aseptic necrosis of the head of the femur or humerus is now successfully managed with the insertion of a bone graft or prosthesis. Exchange transfusions are believed to have prevented recurrent cerebrovascular accidents. The use of prophylactic penicillin and pneumococcal vaccine may have reduced the incidence of sepsis, pneumonia, and meningitis due to susceptible organisms in young children. While this progress can be said to have improved the quality of life of many patients, other complications of sickle cell disease remain as therapeutic dilemmas. The ability to prevent complications is hampered both by a lack of specific therapeutic measures and ignorance as to which patients are likely to develop complications.

Anemia, Sickle Cell↗

Retinal vasculitis and posterior pole "hypopyons" as early signs of acute bacterial endophthalmitis.

PURPOSE: To report a case of acute postoperative bacterial endophthalmitis presenting with retinal vasculitis and posterior pole "hypopyons." DESIGN: Observational case report. METHODS: Observational case report. RESULTS: In a 73-year-old woman, acute postoperative endophthalmitis presented with retinal vasculitis, diffuse retinal hemorrhages, and several posterior pole "hypopyons" that were collections of yellow-white inflammatory debris. The inflammation was located primarily in the posterior one third of the vitreous, and except for severely impaired visual acuity, the classic signs of acute postoperative endophthalmitis were not present until the next day. An immediate pars plana vitrectomy with intravitreal injection of vancomycin, amikacin, and dexamethasone was performed. Vitreous and aqueous cultures grew coagulase-negative Staphylococcus species. After intravenous and topical therapy for endophthalmitis, the inflammation subsided. Eight weeks after the initial cataract surgery, the best corrected visual acuity of the patient was 20/25. CONCLUSION: Acute postoperative bacterial endophthalmitis may present with atypical clinical signs and inflammation located primarily in the retina and posterior vitreous.

Acute Disease↗

Pigmentary irregularities and optic disc edema after heart transplantation.

OBJECTIVES: To determine the prevalence of chorioretinal lesions and optic disc edema after heart transplantation and to study potential associations. DESIGN AND PATIENTS: One hundred one patients who had undergone heart transplantation at one institution and 19 patients prior to heart transplantation underwent ophthalmological examination, including fundus photography. The prevalence of fundus lesions was then compared between the two groups. MAIN OUTCOME MEASURE: With a standardized protocol, the presence of optic disc edema, chorioretinal hyperpigmentation and depigmentation, retinal hemorrhages, cotton-wool lesions, and arteriovenous nicking was graded on color transparencies. RESULTS: The prevalence of optic disc edema and hypopigmentations was significantly higher among the transplant recipients than among the patients prior to heart transplantation (31% vs 5%, P = .01, and 55% vs 11%, P < .001, respectively). Hyperpigmentation was only present in patients after transplantation (15% vs 0%, P = .06). Heart transplant recipients showed an increased risk of hyperpigmentations after 2.5 years. Acute rejection episodes were not associated with posterior pole lesions. CONCLUSION: Common posterior pole lesions after heart transplantation are optic disc edema and pigmentary changes. Although visual acuity does not seem severely impaired, further longitudinal study is necessary to evaluate the long-term significance of these lesions.

Acute Disease↗

Ophthalmologic side effects during alpha-interferon therapy for viral hepatitis.

BACKGROUND/AIMS: Ophthalmologic side effects have been reported during interferon therapy, particularly retinal lesions and neurovisual impairment. The aim of this prospective study was to assess the nature and the frequency of such lesions during alpha-interferon therapy for viral hepatitis. METHODS: Between 1995 and 2003, 156 patients treated with standard or pegylated alpha-interferon, with or without ribavirin, had a regular ophthalmologic examination before and during treatment. No patient had signs of retinopathy before treatment. Cotton-wool spots were found in 31 patients and retinal hemorrhage in nine patients during treatment (24% of patients). These lesions remained asymptomatic and disappeared in all patients. A previous history of arterial hypertension (RR 4.60, 95% CI 1.95-10.85), age above 45 years (RR 2.80, 95% CI 1.36-5.85), and use of pegylated alpha-interferon (RR 2.75, 95% CI 1.41-5.38) were significantly associated with retinopathy. Neurovisual impairment was present in 31 patients (20%) before treatment and in 74 patients (47%) during treatment. CONCLUSIONS: In conclusion, this study showed that signs of retinopathy and neurovisual impairment were common in patients receiving alpha-interferon therapy but were rarely symptomatic. It suggests that alpha-interferon may usually be continued in asymptomatic patients as long as there is careful fundoscopic examination.

Adolescent↗