Fundus autofluorescence imaging findings in retinal pigment epithelial tear.

PURPOSE: Retinal pigment epithelial (RPE) tear is a clinical and angiographic entity, which usually occurs in association with pigment epithelial detachments (PED), in the context of neovascular age-related macular degeneration (ARMD). The recording of fundus autofluorescence (FAF) has been introduced as a technique of retinal imaging, allowing the in vivo assessment of the integrity of RPE. The authors describe the FAF imaging findings in a patient with RPE tear. METHODS: Observational case report. RESULTS: A 70-year-old woman developed RPE tear after the application of photodynamic therapy for choroidal neovascularization associated with PED. The diagnosis of the RPE tear was confirmed by fluorescein angiography (FA) and indocyanine green angiography (ICGA). FAF imaging revealed absence of autofluorescence at the area which was denuded of RPE, while at the area where the RPE was rolled, a heterogeneous signal of FAF was recorded. The intensity of the signal in that area was, on average, not different from the normal background FAF signal expected in an unaffected RPE/photoreceptor complex. CONCLUSIONS: The authors report the FAF imaging findings in a patient with RPE tear. These findings can be interpreted from the ability of FAF imaging to access in vivo the integrity of RPE, and correlate well with the histopathology of this clinical entity. FAF imaging, as a fast and noninvasive technique, may be a useful modality, alternative to FA and ICGA, in the diagnosis and evaluation of such cases. Moreover, it may contribute to a more detailed phenotyping of the various clinical pictures associated with neovascular ARMD.

Advice against smoking is not effective in patients with Graves' ophthalmopathy.

Advice against smoking is one of the means frequently used in the management of patients with Graves' ophthalmopathy (GO). The objective of this study was to prospectively evaluate the efficacy of such advice. The study was performed at a referral centre. Eighty-five smokers out of 102 consecutive patients with GO, who were examined during a 1-year period, were included in the study. Severity of the disease, smoking history, and the results from a patients' self-assessment questionnaire were recorded. The behavioural intervention consisted in a standardized 2-min message from the attending ophthalmologist strongly advising each patient to quit. The main outcome measure was smoking cessation during the 1-year follow-up period. None of the 85 smokers reported smoking cessation either during the follow-up visits or at the end point of the study. The results of our study show that advice against smoking is not effective among patients with GO. Specifically designed intervention programmes may be necessary and should be evaluated in a controlled trial.

Clonazepam associated retinopathy.

PURPOSE: To report a case of retinopathy associated with the longterm intake of the antiepileptic drug clonazepam. METHODS: Case report. RESULTS: A 36-year-old woman, with a history of long-term use of the antiepileptic drug clonazepam developed subtle visual disturbances. Funduscopy revealed areas of mild depigmentation of the retinal pigment epithelium throughout the posterior pole bilaterally corresponding to transmission hyperfluorescence on fluorescein angiography. There was no history of any inherited retinal degenerative disease and no other known agent responsible for retinal toxicity had been used. CONCLUSIONS: The longstanding intake of the antiepileptic drug clonazepam may be associated with the development of toxic retinopathy.

Hypothyroidism and glaucoma. A study of 100 hypothyroid patients.

PURPOSE: To determine whether glaucoma is associated with hypothyroidism, as has previously been suggested. METHODS: This is a cross-sectional study and a noncomparative interventional case series. One hundred consecutive patients with newly diagnosed hypothyroidism were referred for complete ophthalmologic examination, including automated perimetry and examination of the optic disks, to identify the presence of glaucoma. After correction of the hypothyroidism, reexamination was performed. RESULTS: No patient had glaucoma and no correlation was found between intraocular pressure and either thyroid stimulating hormone or free tri-iodothyronine. No statistically significant difference was found between intraocular pressure levels before and after treatment of the hypothyroidism. CONCLUSION: This study does not demonstrate an association between hypothyroidism and glaucoma.

Antioxidant agents in the treatment of Graves' ophthalmopathy.

PURPOSE: To report the effect of antioxidant agents in the treatment of mild and moderately severe Graves' ophthalmopathy. METHODS: Prospective, nonrandomized, comparative study performed at a referral center. A series of 11 patients with mild or moderately severe, active, newly diagnosed Graves' ophthalmopathy were included in the study. Allopurinol (300 mg daily) orally and nicotinamide (300 mg daily) orally were used for 3 months. A complete ophthalmologic examination was performed before and 1 and 3 months after initiation of treatment. The response to treatment was estimated separately for each component of the disease and overall by its effect on a total eye score. Eleven patients with mild or moderately severe, active, newly diagnosed Graves' ophthalmopathy who received placebo were also examined at the same time points. Patients in each group were recruited consecutively. Although nonsmoking was not an exclusion criterion, all patients were cigarette smokers. RESULTS: Nine (82%) of 11 patients treated with oral antioxidants showed improvement of mild to moderately severe Graves' ophthalmopathy versus three (27%) of 11 patients in the control group (P <.05). Soft tissue inflammation was the component of the disease that responded more to treatment. No side effects of antioxidant treatment were recorded. Patients' satisfaction was high. CONCLUSIONS: This pilot study presents encouraging results in the treatment of mild and moderately severe Graves' ophthalmopathy with antioxidant agents. To evaluate these preliminary results, randomized prospec-tive studies are needed.

Central serous chorioretinopathy complicating solar retinopathy treated with glucocorticoids.

BACKGROUND: Solar retinopathy and central serous chorio-retinopathy are two well-defined clinical entities which affect the macular area. Their association has never been described. The relation of central serous chorioretinopathy with the exposure to glucocorticoids has been recently suggested. CASE REPORT: Central serous chorioretinopathy developed in a patient who received corticosteroid therapy for solar retinopathy. CONCLUSION: This case report provides additional evidence that central serous chorioretinopathy may develop under the effect of glucocorticoids. Retinal damage resulting from a previous insult, such as solar retinopathy, may act as the permissive factor.

Distribution and regulation of the optic nerve head tissue PO2.

We investigated the distribution and regulation of the optic nerve head (ONH) tissue partial pressure of oxygen (PO2) under various stimuli and the role of the nitric oxide in the ONH circulation. Tissue PO2 was measured using double-barreled recess microelectrodes in the intact eyes of miniature pigs during normoxia, hyperoxia, hypoxia, variations of systemic blood pressure, and after inhibition of the endothelial nitric oxide synthesis by the administration of nitro-L-arginine. Measurements were performed in front of the ONH at intervascular and juxta-arteriolar areas and at a depth of 50 and 200 microm within the ONH at the center and the rim. During normoxia, PO2 was heterogeneously distributed in the ONH, higher close to the arterioles than in intervascular areas. Hyperoxia induced a significant increase of juxta-arteriolar tissue PO2, while in intervascular areas no change was noticed. Hypoxia did not modify intervascular tissue PO2 at 200 microm depth within the ONH. Variations of the systemic blood pressure did not induce any significant change in ONH tissue PO2. Similarly, no modification was noticed after the administration of nitro-L-arginine. There is a remarkable autoregulatory capacity of the ONH circulation that may compensate for parameters such as hyperoxia, hypoxia, and variations of the systemic blood pressure. Endothelially derived nitric oxide inhibition does not modify the ONH tissue PO2, probably because the tissue PO2 is stabilized by compensatory regulation.

Immune corticotropin-releasing hormone is present in the eyes of and promotes experimental autoimmune uveoretinitis in rodents.

We examined the presence and potential role of local corticotropin-releasing hormone (CRH) in experimental uveitis in rodents. This 41-amino acid peptide, originally isolated from the hypothalamus, is also secreted locally in experimentally induced and natural inflammatory sites, where it exerts autocrine or paracrine proinflammatory effects. Female Lewis rats were immunized with the major pathogenic epitope (R16 peptide) of the interphotoreceptor retinoid-binding protein in complete Freund's adjuvant, monitored daily, and killed 8, 9, 10, 12, 14, or 18 days later, after having developed uveoretinitis. Immunoreactive CRH (IrCRH) was detected by immunohistochemistry in the uveitic eyes in the cytoplasm of inflammatory cells (macrophages, lymphocytes, and polymorphonuclear cells) infiltrating the iris, ciliary body, vitreous, retina, and choroid depending on the stage of the disease. The intensity of the IrCRH staining was positively correlated with the severity of the disease based on morphological criteria. The amount of IrCRH measured by RIA varied between 0.18 +/- 0.03 (mean +/- SE) and 0.79 +/- 0.07 pmol/g wet tissue (8th and 14th day of the disease, respectively). Ophthalmic IrCRH in uveitic rat eyes had similar chromatographic mobility as rat/human CRH-(1-41) by HPLC. Furthermore, female B10.A mice were immunized with interphotoreceptor retinoid-binding protein and treated during the induction (0-7 days) or expression (8-16 days) stages of the disease with ip injections of the anti-CRH antibody TS-2 or placebo nonimmune rabbit serum. The early anti-CRH treatment significantly decreased the disease intensity compared to that in placebo- or late-treated animals (P < 0.05, by analysis of variance). We conclude that IrCRH is present at the site of inflammation in rodent experimental uveitis and that its expression correlates with the natural history and intensity of the disease. Immune CRH appears to play an early pathogenetic role in the induction of experimental uveitis.

Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity.

To determine the spectrum of manifestations in neurofibromatosis 2 (NF2) and to assess possible heterogeneity, we evaluated 63 affected individuals from 32 families. Work-up included skin and neurologic examinations, audiometry, a complete ophthalmology examination with slit-lamp biomicroscopy of the lens and fundus, and gadolinium-enhanced MRI of the brain and, in some, of the spine. Mean age-at-onset in 58 individuals was 20.3 years; initial symptoms resulted from vestibular schwannomas (44.4%), other CNS tumors (22.2%), skin tumors (12.7%), and ocular manifestations including cataracts and retinal hamartomas (12.7%). Five asymptomatic individuals were diagnosed through screening. Vestibular schwannomas were documented in 62 individuals (98.4%); other findings included cataracts (81.0%), skin tumors (67.7%), spinal tumors (67.4%), and meningiomas (49.2%). Usually, clinical manifestations and course were similar within families but differed among families. To assess possible heterogeneity, we assigned affected individuals to three proposed subtypes (representing mild, intermediate, and severe NF2) based on age-at-onset, presence or absence of CNS tumors other than vestibular schwannomas, and presence or absence of retinal hamartomas. Comparisons among the three subtypes for many clinical parameters demonstrated that patients in the mild subtype differed from those in the other two subtypes for most parameters, but that none of the parameters distinguished patients in the intermediate subtype from those in the severe subtype. Thus, there are likely two rather than three subtypes of NF2. Classification of patients to subtype may aid in counseling about long-term prognosis and in formulating individualized guidelines for medical surveillance.

Evoked potential analysis of visual pathways in human albinism.

PURPOSE: To explore the abnormal crossing of the retinogeniculate pathways in human albinos with visual-evoked potentials (VEPs). METHODS: The authors studied the symmetry of the topographic distribution of pattern onset/offset VEPs over the posterior part of the scalp elicited by monocular stimulation of each eye in 31 consecutive patients with different types of albinism. RESULTS: Twenty-one patients had asymmetric responses, with the major amplitude recorded over the lateral part of the scalp contralaterally to the stimulated eye in 14 patients and ipsilaterally in 7 patients. In two patients, the responses had a symmetric topographic distribution. In eight patients, the amplitude was so low that studying the symmetry was not possible. CONCLUSIONS: These findings demonstrate a non-uniform pattern of asymmetry as a result of the miswiring of the visual pathways in human albinism. Moreover, the low amplitude of the VEP recorded in a consecutive series of patients shows the difficulty of the study of this phenomenon in a clinical setting.

Posterior subcapsular cataract in endogenous Cushing syndrome: an uncommon manifestation.

PURPOSE: Posterior subcapsular cataract is a well-known complication of longstanding glucocorticoid therapy (exogenous Cushing syndrome). The purpose of this study was to examine the effect of chronic endogenous hypercortisolism (endogenous Cushing syndrome) on the human lens. METHODS: Sixty consecutive patients (8 to 67 years of age, 46 females, 14 males) with endogenous Cushing syndrome were studied. The exposure to cortisol was estimated based on the duration of the disease and measurements of the 24-hour urine free cortisol excretion. Complete ocular examination included biomicroscopy of the lens after dilation. RESULTS: Duration from the onset of endogenous Cushing syndrome ranged from 1 to 20 years (mean +/- SD, 5.5 +/- 3.7). Urine free cortisol excretion ranged from 250 to 3065 micrograms/24 hr (mean +/- SD, 693 +/- 547; normal values, 20 to 90 micrograms/24 hr). Only two of the 60 patients (3.3%) had posterior subcapsular cataract. This low prevalence contrasts to the high prevalence attributed to glucocorticoid therapy with grossly equivalent total dosage of glucocorticoids. CONCLUSION: It was concluded that posterior subcapsular cataract is an infrequent complication of endogenous hypercortisolism compared to exogenous Cushing syndrome. Because the total exposure to endogenous glucocorticoids was not lower than that of exogenous glucocorticoid therapy, a potential explanation for this difference might be the exposure of the lens to the natural (cortisol) rather than a synthetic glucocorticoid or pharmacokinetic differences of glucocorticoids between the two forms of Cushing syndrome.

Central serous chorioretinopathy in endogenous hypercortisolism.

OBJECTIVE: To examine the potential association of central serous chorioretinopathy with endogenous hypercortisolism (Cushing's syndrome). DESIGN: Ophthalmologic survey of consecutively admitted patients with endogenous Cushing's syndrome. SETTING: An eye clinic of a research center (National Eye Institute, Bethesda, Md). PATIENTS: Sixty consecutive patients with confirmed endogenous Cushing's syndrome. MAIN OUTCOME MEASURES: Findings from complete ophthalmologic evaluation. RESULTS: Three (5%) of 60 patients had one or more episodes of appropriately documented central serous chorioretinopathy. In all cases, the episodes occurred during the period of hypercortisolism. CONCLUSIONS: Central serous chorioretinopathy is an uncommon manifestation of endogenous Cushing's syndrome. Since central serous chorioretinopathy has been associated with other hypercortisolemic states, we suggest that glucocorticoids may play a role in the development of this disease.

Lens opacities in neurofibromatosis 2: further significant correlations.

This prospective study of 96 individuals from 29 families with neurofibromatosis 2, 49 of whom were affected, confirms in an extended series the previously reported association between posterior subcapsular/capsular cataract and neurofibromatosis 2. Posterior subcapsular/capsular cataracts were found in 36 (80%) of the 45 affected individuals (four individuals were excluded from statistical analyses). In addition, the association of peripheral cortical lens opacities with neurofibromatosis 2 was found to be statistically significant. Seventeen of the patients with neurofibromatosis 2 (37.8%) had peripheral cortical cataracts in comparison with none of the unaffected family members (p < 0.0001). In three patients peripheral cortical opacities were present despite the absence of posterior subcapsular/capsular cataracts. These findings support the inclusion of cortical cataracts of early onset, in addition to posterior subcapsular/capsular cataracts, in the diagnostic criteria of neurofibromatosis 2.

Ophthalmologic examination in the diagnosis of Proteus syndrome.

PURPOSE: To describe the clinical features of Proteus syndrome, a rare recently recognized hamartoneoplastic malformation, with emphasis on the ocular findings. METHODS: Complete physical and ocular examination of two new patients with Proteus syndrome. RESULTS: The two reported cases illustrate the wide clinical polymorphism of Proteus syndrome and the overlap of its clinical manifestations with those of other overgrowth syndromes. Both patients had periorbital exostoses and epibulbar tumors. The ocular findings are compared with those in the literature. CONCLUSION: Considering the paucity of information in the ophthalmic literature, this article explores the role of the ophthalmologist in diagnosing this rare entity.

Visual improvement after transethmoid-sphenoid decompression in optic nerve injuries.

Transethmoid-sphenoid decompression has been performed on 11 patients with indirect optic nerve injury. Visual improvement occurred in 8 patients, including 4 patients with initial total blindness. Optic neuropathy improved even when there was a long interval, up to 92 days, between trauma and decompression. There is still controversy about the treatment of traumatic optic neuropathy. Our results suggest that surgery can be helpful in the management of this condition. Transethmoid-sphenoid optic nerve decompression is a minimally invasive procedure that gave, in this series, satisfactory results with low morbidity.