Functional blinking in childhood.

At the Department of Pediatric Ophthalmology, Wills Eye Hospital, 17 children, 18 months to 10 years of age, were seen with a chief complaint of intermittent excessive blinking. Eight (47%) of the patients had been referred for ophthalmologic examination by their pediatrician for evaluation of this symptom. All were in excellent health with no associated symptoms or signs of systemic or ocular disease. None of the children were taking topical ocular or systemic medications. The parents of seven (41%) of these children were able to identify a temporally related stressful event that coincided with the onset of blinking. Durations of the symptom prior to examination ranged from 1 week to 4 months. Spontaneous resolution occurred from one day to 5 months after the first ophthalmologic examination. Recurrence occurred in only one child, but resolution was still completed within 5 months. Excessive eye blinking unassociated with other systemic or ocular findings appears to be a medically benign, self-limited functional disorder.

Inhibition of experimental autoimmune uveoretinitis by oral administration of S-antigen and synthetic peptides.

S-Antigen, a photoreceptor cell protein, is highly efficient in inducing experimental autoimmune uveoretinitis (EAU), a severe inflammation of the uveal tract and retina of the eye. S-Antigen and six synthetic peptides, all of which correspond to known T-cell or B-cell recognition sites, were tested for their ability to induce oral tolerance to EAU in LEW rats. Feeding three 1-mg doses of native S-Antigen or three doses of one synthetic peptide, designated BSA(343-362) (200 micrograms per dose), reduced the incidence and severity of EAU induced by immunization with 50 micrograms of S-Antigen. Another peptide, BSA(270-289), was able to inhibit EAU only when a low dose (10 micrograms) of the uveitogenic S-Antigen was used to induce EAU. Animals which received 200 micrograms doses of four other immunologically active peptides, BSA(31-51), BSA(143-162), BSA(303-327) and BSA(333-352), were not significantly protected. Furthermore, animals fed BSA(343-362) were significantly less susceptible to EAU induced by adoptive transfer (tEAU) of the uveitogenic R9 T-cell lines. Con A-activated lymphocytes purified from spleens of rats fed peptide BSA(343-362) transferred partial resistance to tEAU induced by adoptive transfer of R9 line cells. The resistance of orally tolerized rats to induction of EAU by adoptive transfer of an activated, pathogenic T-cell line, and the ability of lymphocytes from orally-tolerized animals to transfer resistance to tEAU shows that effector mechanisms can be inhibited by oral feeding as well as the afferent mechanisms reported here and elsewhere. Circulating levels of IgG specific for S-Antigen were not affected by feeding any of the peptides.

Impact of delayed treatment in growing posterior uveal melanomas.

OBJECTIVE: To investigate the impact of pretreatment tumor growth on survival in patients with primary posterior uveal melanoma. DESIGN: Retrospective case-by-case matched comparative survival study. PATIENTS: Thirty patients with documented tumor growth of at least 3 mm in basal diameter, 1.5 mm in thickness, or both during a pretreatment interval of 6 months or more and a matched control group of 30 promptly treated patients. Matching criteria included patient age (+/- 10 years), largest basal tumor diameter (+/- 2 mm), tumor thickness (+/- 1.5 mm), location of anterior tumor margin (same defined zone), and visual symptoms (present or absent). SETTING: The Oncology Unit of the Retina Service at Wills Eye Hospital, Philadelphia, Pa. INTERVENTIONS: All patients were treated in a nonrandomized fashion by conventional therapeutic methods appropriate to the tumor's size, location, and other factors. MAIN OUTCOME MEASURES: Actuarial melanoma-specific mortality and all-cause mortality. RESULTS: The mean +/- SE cumulative 5-year probability of melanoma-specific mortality relative to the date of initial examination was 17.1% +/- 7% in the delayed treatment group and 18.4% +/- 8% in the prompt treatment group. This difference is not statistically significant (P > .5, log rank test). CONCLUSIONS: These results lend support to the belief that delayed treatment of selected small and dormant-appearing choroidal and ciliary body melanomas does not substantially increase the probability of melanoma-specific mortality; however, they do not prove that observation is the correct management option for all patients with a posterior uveal melanoma.

Endophthalmitis after pediatric strabismus surgery.

OBJECTIVE: To report 6 cases of endophthalmitis after pediatric strabismus surgery. METHODS: Retrospective review of initial signs, clinical findings, treatment, culture results, and visual and anatomical outcomes in 6 eyes of 6 children treated at 2 tertiary care institutions between 1983 and 1998. RESULTS: Four boys and 2 girls aged 8 months to 6 years (median age, 2 years) developed lethargy and asymmetric eye redness, with or without eyelid swelling or fever, within 4 days of surgery. At diagnosis (median, postoperative day 6) clinical findings included periorbital swelling, redness and leukocoria due to vitritis, and, in some cases, hypopyon. Treatment included pars plana vitrectomy and intravitreal and systemic antibiotics in all cases. Vitreous cultures grew Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. Within 6 months of strabismus surgery, visual acuity was no light perception in all eyes and 3 eyes had been enucleated. The 3 remaining eyes were prephthisical. CONCLUSIONS: Endophthalmitis after pediatric strabismus surgery is rare. Children may not recognize or verbalize symptoms. Causative organisms are virulent. Visual and anatomical outcomes are poor. Lethargy, asymmetric eye redness, eyelid swelling, or fever in the postoperative period, even if initial postoperative examination results are normal, should prompt urgent ocular examination. The diagnosis of endophthalmitis may be made when biomicroscopic or indirect ophthalmoscopic examination confirms the presence of vitreous opacification with or without hypopyon. Arch Ophthalmol. 2000;118:939-944

S-antigen. Identification of human T-cell lymphocyte proliferation sites.

Immune responses to normal retinal proteins, including S-antigen, have been demonstrated in patients with a variety of retinal disorders, as well as in those who have received panretinal laser photocoagulation. T-cell lymphocytes (T cells) have been implicated in the pathogenesis of several ocular inflammatory diseases of possible autoimmune etiology. We used synthetic peptides that correspond to the amino acid sequence of S-antigen in lymphocyte proliferation assays to identify specific sites in the molecule recognized by human T cells. Ten patients with type II diabetes were studied before and after initial panretinal laser photocoagulation for proliferative diabetic retinopathy. T-cell responses, expressed as a stimulation index, to S-antigen and peptides were negative in all patients before treatment. Three weeks after panretinal laser photocoagulation, eight of 10 assays were positive (stimulation index greater than 2; P less than .01) when lymphocytes were stimulated with peptide BSA(273-292); six of nine were positive (P less than .01) with peptide BSA(303-332); and six of six were positive (P less than .001) with peptide BSA(343-362). Our study identifies several specific sites in S-antigen that elicit human immune responses. The implications of these findings with regard to the pathogenesis and treatment of autoimmune uveitis are discussed.

IRBP: preparation and characterization of site-specific monoclonal antibodies.

Interstitial retinoid binding protein (IRBP) is a 136,000 molecular weight photoreceptor cell protein which is a highly pathogenic autoantigen for the induction of experimental autoimmune uveitis (EAU). In this study we produced a series of monoclonal antibodies (MAbs) which define different epitopes in the native molecule. These MAbs were further subdivided into three distinct groups based on a radioimmunoassay, and by ELISA assay using native IRBP and synthetic peptides corresponding to its entire amino acid sequence. Group I MAbs (MAbD7-B1 and MAbC6-B4) bound to native IRBP but not to any synthetic peptides, suggesting that their antigenic epitopes are strictly conformation dependent. Group II MAbs (MAbC7-D3 and MAbG8-H4) bound weakly to multiple peptides which shared amino acid sequence similarity located within each of four homology domains indicating that these epitopes are also conformation dependent. In group III (MAbH3-B5, MAbH7-A5, and MAbB6-D12) MAb binding was localized to a specific peptide. The MAbH3-B5 binding site was further refined to amino acid positions 361 to 367 in the native molecule. MAbH3-B5 was also useful in localizing IRBP in the mouse retina by immunohistochemical techniques. The application of these MAbs in the study of EAU and interphotoreceptor transport mechanisms is discussed.

Ocular telemedicine between Nepal and the USA: prevalence of vitreoretinal disease in rural Nepal.

This study is aimed at reporting experiences with telemedicine between Nepal and the USA and at reporting the prevalence of age-related macular degeneration (AMD) and diabetic retinopathy (DR) in rural Nepal. AMD and DR are becoming more significant factors for non-reversible vision loss in rural Nepal due to increasing life expectancy and urbanisation. The prevalence of DM is low compared with the developed world, but the percentage of diabetics with DR is high, presumably due to limited access to healthcare. The higher prevalence of DM in Hetauda is explained as being due to a more urban lifestyle, dietary habits (more deep-fried food) and more advanced age.

Laser photocoagulation repair of macula-sparing cytomegalovirus-related retinal detachment.

OBJECTIVE: The purpose of the study is to investigate the role of laser photocoagulation in the treatment of macula-sparing cytomegalovirus (CMV)-related retinal detachment (CMVRD) in patients with acquired immune deficiency syndrome (AIDS). DESIGN: Seven macula-sparing CMVRD identified between July 1995 and February 1997 were managed with laser photocoagulation and observed prospectively (group I). Seven CMVRD reattached with pars plana vitrectomy (PPV) and silicone oil injection (group II) between January 1992 and June 1996 were analyzed retrospectively. PARTICIPANTS: Patients with AIDS with macula-sparing rhegmatogenous CMVRD with no proliferative vitreoretinopathy and visual acuity better than 20/30 were studied. INTERVENTION: Demarcation laser photocoagulation (group I) or PPV with silicone oil injection (group II) was performed. MAIN OUTCOME MEASURES: Postoperative best-corrected visual acuity (BCVA), temporary or permanent visual loss, CMVRD progression or recurrence, and cataract were measured. RESULTS: Follow-up ranged from 2 to 19 months (mean, 9 months) in group I. Post-treatment BCVA was unchanged in all eyes after laser. One retina redetached 9 months after laser treatment. Final visual acuity was less than 20/40 in one eye because of progressive CMV retinitis. Follow-up ranged from 2 to 24 months (mean, 10.4 months) in group II. All group II RDs were reattached successfully with PPV and silicone oil injection. Best-corrected visual acuity was an average of 1.6 lines worse after vitrectomy. Silicone-induced hyperopic shift caused temporary visual loss in all eyes (mean duration, 5.6 weeks). Delayed visual loss due to cataract formation occurred in five eyes. Three eyes had cataract extraction within 6 months. Two partial redetachments developed. One was repaired with repeat vitrectomy. Final visual acuity was less than 20/40 in five of seven eyes because of progressive CMV retinitis (1), dense cataract (2), uncorrected refractive error (2), and uncertain cause (1). CONCLUSIONS: Demarcation laser photocoagulation appears to be an effective treatment for many macula-sparing CMVRD. Loss of BCVA, temporary postoperative visual loss due to silicone-induced refractive error, and delayed visual loss due to cataract after vitrectomy with silicone oil injection may be avoided. Demarcation laser photocoagulation may be an effective alternative to vitrectomy in macula-sparing CMVRD.

Advances in the diagnosis and management of AIDS-related eye disease.

AIDS-related eye disease is changing rapidly. New clinical entities have been reported, most numerous of which are the uveitis syndromes in patients with elevated CD4+ counts. Advances in management of cytomegalovirus retinitis (CMVR) include laser demarcation as an alternative to vitrectomy with silicone oil injection in macula-sparing cytomegalovirus-related retinal detachments and discontinuation of maintenance therapy in select patients with quiescent CMVR and elevated CD4+ counts. Screening guidelines have been proposed for childhood CMVR. Serial fundus photography has been recommended to improve follow-up evaluation of CMVR. A method to improve intraocular lens calculation in silicone-filled eyes has been offered. The rapidity and extent to which drug resistant cytomegalovirus infection develops has been elucidated. And the controversy of oral ganciclovir prophylaxis for cytomegalovirus disease has been argued from several angles. The following article reviews these and other advances in the understanding of AIDS-related eye disease.

Ocular manifestations of AIDS.

1. Cytomegalovirus retinitis is the leading cause of AIDS-related blindness. 2. Patients with reduced CD4 counts are at risk of developing cytomegalovirus retinitis and should be informed of symptoms (floaters, scotoma) and should have periodic dilated retina examinations. 3. AIDS patients who develop herpes zoster should be monitored for progressive outer retinal necrosis.

Demarcation laser photocoagulation of selected macula-sparing rhegmatogenous retinal detachments.

OBJECTIVE: To report a series of macula-sparing rhegmatogenous retinal detachments (MSRRDs) treated with demarcation laser photocoagulation (DLP). DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Thirty-one patients (34 eyes) with primary or recurrent MSRRDs without associated visual field loss, necrotizing retinitis, or proliferative vitreoretinopathy (PVR), managed with DLP from November 1992 through May 1999. INTERVENTION: Demarcation laser photocoagulation consisting of a triple row of confluent laser burns. MAIN OUTCOME MEASURES: Best corrected postoperative visual acuity and MSRRD progression or recurrence. RESULTS: Thirty-four primary and recurrent MSRRDs were treated by DLP, which consisted of a triple row of confluent laser burns. Macula-sparing rhegmatogenous retinal detachments were located in all quadrants and affected 10% to 45% of the retina. Findings associated with MSRRDs included lattice degeneration (12 eyes), vitreous hemorrhage (4 eyes), and demarcation line (9 eyes). Symptoms (photopsias or floaters) were associated with 14 MSRRDs. Eight eyes were myopic and 11 were pseudophakic. Thirty-two MSRRDs were shallow, two were dome shaped, and all were smooth without corrugations. Follow-up ranged from 1.5 to 80 months (mean, 15.8 months; median, 17 months). Thirty-three of 34 detachments remained stable after DLP. Three flattened spontaneously. One eye was managed with scleral buckle 6 weeks after DLP. Progression was attributed to incomplete laser treatment. Best corrected postoperative visual acuity was the same or improved in all but one eye, in which a cataract developed. CONCLUSIONS: Demarcation laser photocoagulation is an effective method to manage acute or chronic, primary or recurrent MSRRDs without associated PVR that are shallow and smooth without corrugations. Demarcation laser photocoagulation is an alternative to both observation and surgical repair for these select MSRRDs.

Discontinuation of maintenance therapy in patients with quiescent cytomegalovirus retinitis and elevated CD4+ counts.

OBJECTIVE: To determine whether maintenance therapy can be discontinued safety in patients with quiescent cytomegalovirus retinitis (CMVR) and increased CD4+ counts after treatment with highly active antiretroviral therapy (HAART). DESIGN: A prospective observational case series. PARTICIPANTS: Eight human immunodeficiency virus (HIV)-positive patients with quiescent CMVR who were taking HAART and had CD4+ counts above 100 cells/microliter elected to discontinue anti-CMV maintenance treatment. INTERVENTION: Biweekly-to-monthly indirect ophthalmoscopy and fundus photographs, monthly-to-quarterly CD4+ counts, and quarterly HIV viral loads were ordered. MAIN OUTCOME MEASURES: Twelve previously affected eyes were examined for evidence of recurrent retinitis, which was defined as any retinal whitening, border opacification, or expansion of areas of retinal pigment epithelial (RPE) atrophy greater than 750 microns. Four previously unaffected fellow eyes were observed for new CMVR. RESULTS: There was no reactivation or progression of retinitis in any patient during the mean follow-up interval of 11.4 months (range, 3-16 months). No previously unaffected eye developed CMVR. CD4+ remained elevated in all patients (range, 70-725; mean, 255). The HIV viral load ranged from undetectable to 139,000 copies. CONCLUSION: Discontinuation of maintenance therapy may be considered in patients with HAART-induced elevated CD4+ counts above 100 cells/microliter, prolonged relapse-free intervals during the reconstitution period before CD4+ counts rise above 100 cells/microliter, and completely quiescent retinitis characterized by RPE scarring only. Reduced risks of drug toxicity and drug-resistant organisms are potential benefits. Close observation for evidence of recurrent retinitis is indicated.

Intermittent obstructive hydrocephalus in the Arnold-Chiari malformation.

A 26-year-old woman with a Chiari-I malformation and intermittent symptoms of intracranial pressure elevation is described. Clinically, papilledema was accompanied by midperipheral retinal hemorrhages. Repeat computed tomographic scans and lumbar puncture showed normal results. Posterior fossa-directed magnetic resonance image scanning revealed the Chiari-I malformation. Intraventricular monitoring was necessary to demonstrate the marked but unsustained elevation of intracranial pressure.

Cryotherapy for retinopathy of prematurity: a histopathologic comparison of a treated and untreated eye.

A female infant born at 28 weeks gestational age, weighing 570 g, developed retinopathy of prematurity (ROP) which progressed to threshold disease in one eye. Transscleral cryotherapy of the avascular peripheral retina resulted in complete clinical regression of the active ROP in that eye. The fellow eye continued to manifest subthreshold ROP. Histopathologic findings included a striking reduction of the cryotreated retina to a thin glial scar, with associated retinal pigment epithelium atrophy, denudation of Bruch's membrane, and extensive atrophy of the underlying choroidal vasculature, predominantly the choriocapillaris.

Impact of local tumor relapse on patient survival after cobalt 60 plaque radiotherapy.

The authors investigated the impact of local intraocular tumor relapse on survival in a matched-group comparison study of patients with primary choroidal or ciliary body melanoma managed with cobalt 60 plaque radiotherapy. Sixty-two patients with local relapse were matched with an equal number of relapse-free patients in terms of known clinical prognostic factors for both melanoma-specific mortality (largest linear tumor dimension, location of anterior tumor margin, age) and local tumor relapse (location of posterior tumor margin). The follow-up of every relapse-free patient equaled or exceeded the interval to relapse for each matched patient with local relapse. The estimated 5-year survival (Kaplan-Meier) in the relapse-free patients was 87% (standard error = 4%), while that in the local relapse group was 58% (standard error = 6%). This difference is statistically significant (P less than 0.0001, log rank test). These results support the hypothesis that local tumor relapse after cobalt 60 plaque radiotherapy is an important post-treatment clinical indicator of the tumor's greater malignant potential and the patient's increased risk of melanoma-specific mortality.

Taches de bougie.

BACKGROUND: Posterior segment lesions, including taches de bougie, may be the presenting sign of sarcoidosis. In patients with unrecognized sarcoidosis, taches de bougie may be misinterpreted as the lesions of birdshot chorioretinopathy (BCR) or multifocal choroiditis (MFC). METHODS: In a retrospective study, the authors identified 22 patients with taches de bougie and sarcoidosis. A tissue biopsy showed noncaseating granulomas in 17 patients. All available ophthalmic and medical records of these patients were reviewed. RESULTS: Two patterns of taches de bougie were observed. Sixteen patients (73%) had small, discrete white spots in the inferior or nasal periphery, indistinguishable from the lesions of MFC. In six patients (27%), larger, posterior, pale yellow-orange streaks developed that were identical to the lesions of BCR. Visual prognosis was better with posterior streaks. The chest x-ray was normal in 5 of 16 patients with peripheral spots and in 3 of 6 patients with posterior streaks. Serum angiotensin-converting enzyme was negative in 5 of 14 patients. Gallium scan showed increased hilar uptake in five patients, three of whom had a normal chest x-ray. Human lymphocyte antigen A29 was positive in one of nine patients. CONCLUSIONS: Sarcoidosis should be considered in patients with fundus findings that resemble BCR or MFC. Initial evaluation should include chest x-ray and testing the angiotensin-converting enzyme level. These test results may be negative in patients outside the 20- to 40-year age group for typical sarcoid. Further evaluation with nondirected conjunctival biopsy and whole-body gallium scan may be indicated in certain patients, including (1) those with BCR or MFC with normal chest x-ray and elevated angiotensin-converting enzyme level; (2) patients older than 50 years with MFC; or (3) human lymphocyte antigen A29-negative BCR.

Reversible visual loss in a patient receiving high-dose ciprofloxacin hydrochloride (Cipro)

Bilateral acute visual loss characterized by cecocentral scotomas and acquired dyschromatopsia developed in a patient receiving large oral doses of ciprofloxacin hydrochloride (Cipro). The visual defects improved after cessation of this antibiotic. To our knowledge, this association has not been described previously. The use of this medication in high doses must be accompanied by careful monitoring of optic nerve function.