Origin and turnover of ECM proteins from the inner limiting membrane and vitreous body.

The inner limiting membrane (ILM) and the vitreous body (VB) are two major extracellular matrix (ECM) structures that are essential for early eye development. The ILM is considered to be the basement membrane of the retinal neuroepithelium, yet in situ hybridization and chick/quail transplant experiments in organ-cultured eyes showed that all components critical for ILM assembly, such as laminin or collagen IV, are not synthesized by the retina. Rather, ILM proteins, with the exception of agrin, originate from the lens or (and) ciliary body and are shed into the vitreous. The VB serves as a reservoir providing high concentrations of ILM proteins for the instant assembly of new ILM during rapid embryonic eye growth. The function of the retina in ILM assembly is to provide the cellular receptor proteins for the binding of the ILM proteins from the vitreous. The VB is a gelatinous ECM structure that fills the vitreous cavity of the eye. Its major structural proteins, collagen II and fibrillin, originate primarily from the ciliary body. Reverse transcription-PCR and western blotting show that the rate of synthesis of structural, monomeric ILM and VB proteins, such as laminin, collagen IV and II is very high during embryogenesis and very low in the adult. The downregulation of ILM and VB protein synthesis occurs during early postnatal life, and both ILM and VB are from then on maintained throughout life with minimum turnover. Our data explain why ILM and VB do not regenerate after vitrectomy and ILM peeling.

Age-related maculopathy: an expanded genome-wide scan with evidence of susceptibility loci within the 1q31 and 17q25 regions.

PURPOSE: We seek to identify genetic loci that contribute to age-related maculopathy susceptibility. METHODS: Families consisting of at least two siblings affected by age-related maculopathy were ascertained using eye care records and fundus photographs. Additional family members were used to increase the power to detect linkage. Microsatellite genotyping was conducted by the National Heart, Lung and Blood Institute Mammalian Genotyping Service and the National Institutes of Health Center for Inherited Disease Research. Linkage analyses were conducted with parametric (autosomal dominant; heterogeneity lod score) and nonparametric methods (S(all) statistic) using three diagnostic models. False-positive rates were determined from simulations using actual pedigrees and genotyping data. RESULTS: Under our least stringent diagnostic model, model C, 860 affected individuals from 391 families (452 sib pairs) were genotyped. Sixty-five percent of the affected individuals had evidence of exudative disease. Four regions, 1q31, 9p13, 10q26, and 17q25, showed multipoint heterogeneity lod scores or S(all) scores of 2.0 or greater (under at least one model). Under our most stringent diagnostic model, model A, the 1q31 heterogeneity lod score was 2.46 between D1S1660 and D1S1647. Under model C, the 17q25 heterogeneity lod score at D17S928 was 3.16. Using a threshold of 1.5, additional loci on chromosomes 2 and 12 were identified. CONCLUSIONS: The locus on chromosome 1q31 independently confirms a report by Klein and associates mapping an age-related maculopathy susceptibility gene to this region. Simulations indicate that the 1q31 and 17q25 loci are unlikely to be false positives. There was no evidence that other known macular or retinal dystrophy candidate gene regions are major contributors to the genetics of age-related maculopathy.

Laser pneumatic retinopexy for repair of recurrent retinal detachment after failed scleral buckle--ten years experience.

BACKGROUND: Although pneumatic retinopexy was introduced for the repair of primary retinal detachments, we have had excellent long-term success in employing this technique along with laser photocoagulation following failure of routine scleral buckle surgery in nonvitrectomized eyes over the last 10 years. PATIENTS AND METHODS: We categorized a consecutive series of 40 eyes that failed primary scleral buckling surgery and had at least six months follow-up. Eyes were separated into two groups: those with 1) subretinal fluid persisting or developing during the first 14 days after surgery or 2) those accumulating subretinal fluid at least 14 days after initially successful anatomic reattachment of the retina. RESULTS: In these groups, 36 of the 40 eyes (90%) were successfully reattached using outpatient pneumatic retinopexy alone. Complications were limited to the production of new retinal breaks in 5 patients. The 4 pneumatic retinopexy failures were all subsequently treated successfully with either scleral buckle revision or vitrectomy. CONCLUSION: We believe that laser pneumatic retinopexy repair of recurrent retinal detachments following scleral buckle and without significant proliferation vitreoretinopathy (PVR) should be considered ahead of conventional surgical intraoperative techniques. Laser pneumatic retinopexy may be a very successful procedure for the treatment of recurrent retinal detachments after failed scleral buckle surgery. In a consecutive series of 40 eyes with recurrent retinal detachment, we were able to repair 36 with pneumatic retinopexy alone.

Migration of silicone oil into the brain: a complication of intraocular silicone oil for retinal tamponade.

PURPOSE: To report a case in which intravitreal silicone oil migrated along the intracranial portion of the optic nerve and into the lateral ventricles of the brain after the repair of a retinal detachment secondary to cytomegalovirus retinitis. METHODS: A 42-year-old man with acquired immunodeficiency syndrome (AIDS) developed a rhegmatogenous retinal detachment in his left eye secondary to a cytomegalovirus infection of the retina. The detachment was repaired using 5000 cs intraocular silicone oil for a long-term tamponade. Subsequently, the affected eye developed glaucoma, which was poorly controlled. Fifteen months after the retinal surgery, he developed a peripheral neuropathy that was thought to be AIDS related. Computed tomography and magnetic resonance imaging of the head were performed to investigate the neuropathy. RESULTS: The patient was found to have a foreign substance within his lateral ventricles that shifted with position and was identical with respect to its imaging properties to the remaining intraocular silicone oil. Additional material was found along the intracranial portion of his optic nerve. CONCLUSION: Under certain circumstances, intraocular silicone oil may migrate out of the eye, along the intracranial portion of the optic nerve, and into the lateral ventricles of the brain.

Peripheral retinal neovascularization (Eales disease) associated with the factor V Leiden mutation.

PURPOSE: To illustrate a case of peripheral retinal neovascularization (Eales disease) in a patient who tested positive for the factor V Leiden mutation. METHODS: A 42-year-old woman had a 1-week history of blurred vision in her right eye. Her medical history was remarkable for a cerebrovascular accident. Ophthalmoscopy of the right eye disclosed a mild vitreous hemorrhage and a ridge of retinal neovascularization in the temporal periphery. The left fundus showed evidence of temporal retinal ischemia. A laboratory evaluation for hypercoagulability was positive for factor V Leiden mutation. RESULTS: Peripheral scatter laser photocoagulation was applied to the ischemic retina, and the neovascularization regressed. The patient began taking warfarin sodium to prevent further thrombotic events. CONCLUSION: A laboratory evaluation for coagulopathy, including the factor V Leiden mutation, should be added to the examination of patients with Eales disease, especially individuals with a history of a previous thrombotic event.

Time-kill profiles of Enterococcus to antibiotics used for intravitreal therapy.

BACKGROUND AND OBJECTIVE: To determine and then compare the time-kill profiles of Enterococcus to antibiotics used for intravitreal therapy. PATIENTS AND METHODS: The time-kill profiles of four endophthalmitis isolates of Enterococcus faecalis, one vancomycin-resistant E. faecalis isolate, and three vancomycin-resistant isolates of E. faecium were determined against vancomycin, amikacin, cefazolin, gentamicin, ampicillin, ciprofloxacin, ceftazidime, clindamycin, and the combinations of vancomycin and amikacin, vancomycin and ceftazidime, vancomycin and gentamicin, vancomycin and ampicillin, cefazolin and gentamicin, and ampicillin and gentamicin. RESULTS: No single antibiotic or combination was bactericidal (defined as 99.9% kill) to all isolates of Enterococcus. Gentamicin was bactericidal to all E. faecalis isolates. None of the tested antibiotics were bactericidal to vancomycin-resistant E. faecium. CONCLUSIONS: The time-kill profiles demonstrated that vancomycin and ceftazidime did not produce a 99.9% kill for E. faecalis in this small study. Gentamicin combined with either cefazolin or ampicillin had somewhat better bactericidal activity and should be considered as an alternative therapy. Novel therapy may be necessary to treat endophthalmitis because of vancomycin-resistant Enterococcus, depending on the susceptibility patterns of the individual isolate and the response to initial therapy.

AIDS and the eye.

The AIDS pandemic has finally emerged from the big cities to the small towns of this country, as patients with this disease are returning home to spend their last months and days in the care of their families. No physician will be spared from caring for patients with AIDS. This multisystem disease crosses the boundaries of primary and specialty medicine, and with its various manifestations, presents to virtually all health care professionals. This infection has an enormous impact on our society: economically, socially, and medically. The seriousness of this condition is reflected in the medical school curriculum at the University of Pittsburgh. AIDS education begins the first day of the first year for our medical students.

Miyake analysis of anterior vitrectomy techniques.

PURPOSE: To study the efficacy and safety of anterior vitrectomy with the Miyake system. SETTING: Miyake Laboratory, IOLAB, Claremont, California. METHODS: Four pig eyes and three human eyes were transected equatorially. The anterior segments were glued to a glass slide and placed on a stage for anterior and posterior videography. Phacoemulsification was performed, and the posterior capsule was intentionally ruptured. Three different vitrectomy techniques were studied: anterior vitrectomy with coaxial infusion sleeve, anterior vitrectomy with separate limbal infusion, and pars plana vitrectomy with limbal infusion. RESULTS: All techniques showed that vitreous could be safely and effectively removed without undue stress on the retina whenever the vitrectomy instrument was held directly beneath the iris and not placed peripherally to the iris root. Only the pars plana site allowed access to the entire posterior aspect of the iris for removal of vitreous gel. CONCLUSION: Anterior vitrectomy can be performed safely and effectively with any of the three approaches studied. The pars plana technique permitted removal of gel beneath the superior iris. This has important clinical implications because iridovitreous adhesions tend to form superiorly after limbal vitrectomy.

Prevalence of lens changes in Ukrainian children residing around Chernobyl.

The objective of this study is to determine the prevalence and characteristics of lens changes in the eyes of a pediatric population, 5-17 y old, living in the permanent control zone around the Chernobyl nuclear reactor and to compare these findings with those from an unexposed control population. A total of 1,787 children are reported on (996 exposed and 791 unexposed). Over three-quarters of the subjects examined in this study show a form of minor change, termed focal lens defect, in the cortical and/or nuclear portions of the lens of the eye. The exposed group shows a small (3.6%), but statistically significant excess (p = 0.0005) of subclinical posterior subcapsular lens changes similar in form to changes identified in atomic bomb survivors. These posterior subcapsular changes tend to occur in boys 12-17 y old and in exposed children who report consuming locally grown mushrooms on a regular basis.

Subretinal neovascularization in children and adolescents.

Subretinal neovascular membranes (SRNVM) in the pediatric population are rare. The clinical presentation, etiology, course, and management of SRNVM in 25 children (27 eyes) were studied retrospectively. Inflammatory or infectious conditions predominated (10 of 25). Eleven of 19 untreated SRNVM (58%) spontaneously involuted, with 9 of these 11 achieving a final visual acuity of 20/50 or better. A hyperpigmented ring on fluorescein angiography was associated with 9 of the 11 involuted SRNVM. The presence of this pigmented ring may help to identify those cases with a better visual prognosis.

Antihistamines reduce blood-retinal barrier permeability in type I (insulin-dependent) diabetic patients with nonproliferative retinopathy. A pilot study.

PURPOSE: To determine if histamine receptor stimulation mediates increased blood-retinal barrier (BRB) permeability in patients with diabetic retinopathy, as it does in experimental diabetes. METHODS: Fourteen patients with type I (insulin-dependent) diabetes and mild nonproliferative diabetic retinopathy were treated with combined astemizole, 20 mg, and ranitidine, 600 mg, or an identical placebo for 6 months in a double-masked fashion. Blood-retinal barrier permeability was measured by vitreous fluorometry at baseline and at 3 and 6 months. RESULTS: Permeability was significantly reduced in the group treated with antihistamines (P < 0.05) compared with the placebo group. There were no concomitant significant changes in systemic arterial blood pressure or HbA1c values. CONCLUSION: These pilot data suggest that histamine receptors influence permeability of the BRB in human diabetes. Further studies of the effects of antihistamines on diabetic retinopathy are warranted.

Intraocular candidiasis in patients with candidemia. Clinical implications derived from a prospective multicenter study.

PURPOSE: Intraocular infection caused by Candida species can have devastating visual consequences. With the emergence of Candida as a major nosocomial pathogen, the authors investigated the prevalence of ocular lesions in patients with candidemia and evaluated risk factors for eye involvement. METHODS: This study is a prospective, multicentered, observational design. One hundred eighteen patients with candidemia were evaluated by the infectious disease service and received indirect ophthalmologic examination within 72 hours of a reported positive blood culture. Ocular findings were classified on the basis of objective, pre-determined criteria. Candida chorioretinitis was defined as the presence of focal, white, infiltrative chorioretinal lesions without vitreal involvement. Candida endophthalmitis was defined as chorioretinitis with extension into the vitreous or intravitreal "fluff balls." RESULTS: In contrast to previous studies of patients with candidemia citing prevalence rates of endophthalmitis approaching 40%, no patients were shown to have endophthalmitis. Candida chorioretinitis was seen in 9% of the patients, all of whom received antifungal agents. The observation that chorioretinitis never progressed to endophthalmitis suggests that systemic antifungal agents provided adequate ocular therapy. Risk factors for Candida chorioretinitis include fungemia with Candida albicans (versus nonalbicans species), multiple positive blood cultures, visual symptoms, and immunosuppression. Twenty percent of patients had nonspecific ocular lesions not directly related to infection. CONCLUSION: Patients with candidemia who have the risk factors noted above warrant formal ophthalmologic examination.

Empiric treatment of endophthalmitis. Are aminoglycosides necessary?

OBJECTIVE: To reevaluate the necessity of empiric gram-negative therapy for postoperative endophthalmitis based on the recognition of aminoglycoside-induced toxic effects. METHODS: A review of 162 cases of culture-positive bacterial endophthalmitis to determine bacterial prevalence, antibiotic susceptibilities, and laboratory staining results of intraocular material. RESULTS: One hundred fifty (93%) gram-positive and 12 (7%) gram-negative isolates. All the gram-positive bacteria were susceptible to vancomycin hydrochloride; and gram-negative bacteria were susceptible to gentamicin sulfate, amikacin sulfate, and ceftazidime sodium. Bacterial rods were observed on smear of intraocular material in 10 gram-negative cases submitted for examination. CONCLUSION: Vancomycin is an appropriate single agent if laboratory studies rule out gram-negative infection. In the absence of laboratory support, an aminoglycoside (possible toxic effects) or another gram-negative antibiotic (possibly ceftazidime) should also be administered.

The role of ciprofloxacin in endophthalmitis therapy.

Ciprofloxacin has been proposed for the systemic treatment of endophthalmitis. We studied the role of therapy based on the susceptibility of actual bacterial isolates and developed a system for assessing this susceptibility in endophthalmitis. Susceptibility testing was performed on 68 bacterial isolates from 66 patients with endophthalmitis. Our results indicated that, on the basis of a vitreous ciprofloxacin concentration of 0.25 microgram/ml, only 41 of 68 isolates (60%) would be inhibited by systemic therapy. All gram-negative bacteria (six of six) would be inhibited, whereas gram-positive bacterial susceptibility was variable. We concluded that systemic ciprofloxacin alone should not be administered empirically but it could provide an adjunct for treating selective cases of bacterial endophthalmitis. Bacterial susceptibility should be assessed on a blood serum standard of 0.25 microgram/ml instead of 1.0 microgram/ml.

Prediction of visual recovery after scleral buckling of macula-off retinal detachments.

Patients with rhegmatogenous retinal detachments involving the fovea have visual loss that may not be recoverable despite anatomically successful surgery. Few guidelines exist to predict ultimate visual outcome with any certainty. We found that despite macular detachment, a device commonly used to predict visual acuity in cataractous eyes, the Potential Acuity Meter (Mentor O & O, Inc., Norwell, Massachusetts), provided acuity measurements even when Snellen visual acuity levels were poor or unmeasurable. In a study of 50 consecutive patients with clear media, we investigated a possible correlation between postoperative Snellen visual acuity with the preoperative Potential Acuity Meter results. We found that actual visual improvement correlated well with potential visual improvement as determined by Potential Acuity Meter measurements (R = .92). Preoperative assessment of patients with this device was a better predictor of final visual outcome than preoperative Snellen visual acuity, the extent of retinal detachment, or the duration of the retinal detachment by history.

A survey of intraocular silicone oil use in the United States.

PURPOSE: This survey was conducted to determine the pattern of usage of intravitreal silicone oil in the United States. METHODS: A questionnaire was sent to 542 members of the Retina and Vitreous Societies in December 1990, and again 6 weeks later in an attempt to improve the response rate. RESULTS: Two hundred eighty-seven questionnaires (53%) were returned. Ninety-eight percent of the respondents perform vitreous surgery, and 61% of them use silicone oil. This survey determined the degree of participation in Food and Drug Administration (FDA)- and institutional review board-approved protocols and the most common indications for use of silicone oil. Ninety-six percent of the respondents indicated that the use of silicone oil represented an acceptable standard of care. CONCLUSION: Silicone oil is widely used in the United States despite its lack of FDA approval.