Finasteride is effective for the treatment of central serous chorioretinopathy.

PurposeTo evaluate the safety and efficacy of finasteride treatment in patients with central serous chorioretinopathy (CSC).MethodsRetrospective review of 29 eyes of 23 patients who were treated with finasteride for CSC. Previous medical and ocular history, steroid use, length of finasteride treatment, additional treatments for CSC, visual acuity (VA), central macular thickness (CMT), and presence of subretinal fluid (SRF) throughout the follow-up period, and the occurrence of any complications were recorded.ResultsInitial VA was 0.29±0.31 logMAR, and a trend towards improved VA was noted after 3 months (0.25±0.36 logMAR; P=0.07). VA was significantly improved at the final follow-up (0.23±0.27 logMAR; P=0.024). Initial CMT was 354±160 µm, and was significantly reduced after 1 month of treatment (284±77 µm; P=0.002) and this was maintained to the end of follow-up (247±85 µm; P=0.001). A significant reduction in SRF presence was found at all time points, with an overall 75.9% rate of complete resolution. Following discontinuation, SRF recurrence was noted in 37.5% of cases. No adverse events were recorded.ConclusionsFinasteride is a safe and effective treatment for CSC. It may be a possible new option for the initial management of patient with CSC, and a suggested treatment approach is presented.

Evaluation of internet websites about retinopathy of prematurity patient education.

BACKGROUND/AIMS: The success of the treatment in patients with retinopathy of prematurity (ROP) is mainly associated with timely diagnosis and appropriate management. Information dissemination is crucial for the outcome of ROP. This study aimed to evaluate the quality of the information about ROP available for patients on the internet. METHODS: Cross sectional study. In March 2004 the ROP information available on the internet was evaluated using two search engines (MetaCrawler and MSN) and four key terms ("retinopathy of prematurity," "premature eye," "premature retina," and "ROP"). The quality of each website was evaluated using a score system. The sites were classified as academic, organisational, or commercial. Readability, general quality of the website (based on ownership, purpose, authorship, author qualification, attribution, interactivity, and currency), and quality of the content specific to ROP (definition, causes, epidemiology, risk factors, diagnosis, classification, treatment, and prognosis) were analysed. RESULTS: Of 114 websites evaluated, 40 were included. 10 sites (25.0%) were academic, eight (20.0%) organisational, and 22 (55.0%) commercial. In the majority of the sites (62.5%) the ROP information was fair or poor. CONCLUSIONS: A large amount of information about ROP is available on the internet. However, most websites were considered incomplete.

Ceramide: a potential mediator of apoptosis in human retinal pigment epithelial cells.

PURPOSE: To investigate the signal transduction mechanisms involved in the cell death of human retinal pigment epithelial (RPE) cells after their exposure to either hydrogen peroxide (H(2)O(2)) or tri-butyl hydroxperoxide (tBH). METHODS: Cultured human RPE (hRPE) cells were treated with the chemical oxidants tBH and H(2)O(2) as well as with the synthetic ceramide analogs C(2), C(6), and dihydroceramide for different time periods. Apoptosis was determined by TUNEL staining and annexin-V labeling of phosphatidylserine exposure. Ceramide levels were quantified by the diacylglycerol kinase assay using thin-layer chromatography. RESULTS: H(2)O(2) and tBH caused a high level of apoptosis in the hRPE cells. At the same time, both of these oxidants induced an early and late increase in the intracellular production of ceramide, a lipid second messenger. Moreover, addition of C(2) and C(6) synthetic ceramides caused a high level of apoptosis in these hRPE cells. In contrast, treatment with the immediate precursor of ceramide, dihydroceramide, resulted in no apoptotic response. CONCLUSIONS: The results demonstrate that H(2)O(2) and tBH induce apoptosis in hRPE cells and suggest that the underlying signaling mechanism involves ceramide generation.

Expression of fibroblast growth factor-5 by bovine choroidal endothelial cells in vitro.

PURPOSE: To demonstrate the expression of fibroblast growth factor-5 (FGF-5) by bovine choroidal microvascular endothelial (BCME) cells and to investigate its possible role as an autocrine mitogen in these cells. METHODS: Expression of FGF-5 by BCME cells was studied by a combination of Northern and Western blot analyses. Total RNA was isolated from BCME cultures at passages 5 through 8 and analyzed by Northern blot analysis for the presence of FGF-5 transcripts, using a 1-kb human complemetary DNA. Slot-blot analysis was performed to determine possible cross-reactivity between this probe and acidic and basic FGFs of human and bovine species. A previously characterized antibody directed against the aminoterminus of the human FGF-5 sequence was used in Western blot analyses to identify immunoreactive proteins released by BCME cells into the medium. Finally, the mitogenic activity of human recombinant FGF-5 on a variety of cell types was evaluated, using a cellular proliferation assay. RESULTS: Northern blot analysis provided evidence for the expression of two major FGF-5 transcripts at 4 kb and 3 kb and two minor transcripts at 2.2 kb and 1.7 kb. A single immunoreactive protein with a molecular weight of 34 kDa was identified by Western blot analysis of conditioned media. In cellular proliferation assays, human recombinant FGF-5 was not mitogenic in BCME cells but exhibited an approximate ED50 of 1.8 to 3.7 nM in BALB/c3T3 fibroblasts. This ED50 was within the range reported by the manufacturer, using a thymidine incorporation assay and a similar embryonic fibroblast cell line. Fibroblast growth factor-5 also stimulated proliferation of human retinal pigment epithelial cells. CONCLUSIONS: Bovine choroidal microvascular endothelial cells exhibit expression in vitro of FGF-5 at the messenger RNA and protein levels. Perivascular and endothelial cell staining for FGF-5 seen previously in choroidal neovascular membranes may therefore arise from expression by choroidal endothelial cells. Because nonglycosylated recombinant FGF-5 does not appear to be a mitogen in BCME cells in vitro, it is reasonable to question its role as an autocrine mitogen in vivo. Fibroblast growth factor-5 may instead be serving paracrine roles in the stimulation of fibroblasts and retinal pigment epithelial cells during the formation of choroidal neovascular membranes. Studies with fully glycosylated recombinant FGF-5 will be required, however, to assess the biologic activity of this member of the FGF gene family.

Age and topographic variation of insulin-like growth factor-binding protein 2 in the human rpe.

PURPOSE: Previous studies have shown that insulin-like growth factor-binding protein (IGFBP)-2 is markedly upregulated in senescent RPE cells in vitro, and might therefore be a marker of senescent cells in vivo. This study was conducted to determine whether IGFBP-2 expression in human RPE cells from the macula and periphery varies with age in vivo. METHODS: Paraformaldehyde (4%)-fixed and optimal cutting temperature (OCT) compound-embedded human eyes from 17 patients were cryosectioned and subjected to high-sensitivity digoxigenin (DIG)-labeled cRNA in situ hybridization to determine the expression of IGFBP-2. Complementary immunohistochemistry experiments using a polyclonal anti-IGFBP-2 antibody were performed to confirm IGFBP-2 protein expression. Specimens were examined by light microscopy, and images were captured with a digital camera. The total numbers of RPE cells and IGFBP-2 mRNA expression-positive RPE cells were counted for each section, and the ratio of labeled RPE cells to total RPE cells counted was calculated for both macular and peripheral regions of each donor. RESULTS: IGFBP-2 mRNA expression was detected in the ganglion cell layer, inner and outer nuclear layers, and inner segments of photoreceptor cells in all 17 eyes. In 16 of 17 eyes, IGFBP-2 mRNA expression was detected in the RPE. In 11, the ratio of labeled cells to total RPE cells counted per section in the macula was 1.2 times greater than the ratio in the periphery (P = 0.008). The ratio of labeled RPE cells in the macula decreased with age (P = 0.0064). Immunohistochemistry studies for IGFBP-2 confirmed the expression pattern found by in situ hybridization. CONCLUSIONS: There is a topographical and age-related change in IGFBP-2 expression in RPE cells from human donor eyes. This distribution is likely not to represent senescent RPE cells in vivo.

Senescence-associated beta-galactosidase histochemistry for the primate eye.

PURPOSE: To develop a senescence-associated beta-galactosidase histochemistry and bleaching protocol for the primate posterior pole. METHODS: Rhesus monkey eyes of different ages were enucleated after death, fixed in 4% paraformaldehyde for up to 16 hours, and cryoprotected using a graded sucrose infiltration technique. Ten-micrometer tissue sections were treated with beta-galactosidase, pH 4 (lysosomal) or pH 6 (senescence-associated) activity, for various times. Bleaching of retinal pigment epithelial (RPE) cell and choroidal melanocyte pigment was performed after beta-galactosidase histochemistry using 0.1% to 1% potassium permanganate incubation for 1 minute to 2 hours followed by 0.5% oxalic acid immersion. RESULTS: A 6-hour incubation with beta-galactosidase, pH 4 or 6, demonstrated optimal staining of the RPE. Uniform staining of the RPE for pH 4 beta-galactosidase was seen in both young and old eyes. In contrast, senescence-associated beta-galactosidase (pH 6) staining was seen in the RPE of 16 and 29-year-old, but not 1- and 2-year-old eyes. Senescence-associated beta-galactosidase staining was evident in RPE cells adjacent to cuticular drusen. Optimal bleaching without loss of beta-galactosidase staining was obtained using a 25-minute incubation with 0.05% permanganate. CONCLUSIONS: The senescence-associated beta-galactosidase histochemistry assay, adapted for use in the primate posterior pole, showed staining of RPE cells in older eyes. Visualization of beta-galactosidase activity in the RPE was enhanced by permanganate bleaching of melanin pigment. This technique could be valuable for identifying senescent RPE cells in human eyes.

Bovine retinal pigment epithelium promotes proliferation of choroidal endothelium in vitro.

The invasion of Bruch's membrane and subsequently the subpigment epithelium and subretinal spaces by proliferating choroidal capillaries is a prominent feature of age-related macular degeneration. The ability to isolate and propagate pure cultures of bovine choroidal microvascular endothelium, choroidal pericytes, turbinate fibroblasts, and bovine retinal pigment epithelium allowed us to identify a growth-promoting activity produced by the retinal pigment epithelium that stimulated the proliferation of these cells in vitro. This mitogenic activity is present in both retinal pigment epithelium-conditioned medium and retinal pigment epithelium extract and enhances the mitogenic activity of retinal-derived extract. The activity is resistant to extremes of temperature and pH but partially sensitive to trypsin inactivation.

Evaluation of a commercial recombinant tissue-type plasminogen activator preparation in the subretinal space of the cat.

To explore the feasibility of using human recombinant tissue-type plasminogen activator in the management of subretinal hemorrhage, we examined the toxic effects of a commercial preparation of human recombinant tissue-type plasminogen activator in the subretinal space of the holangiotic retina of the cat. Various concentrations of human recombinant tissue-type plasminogen activator and controls were infused into the subretinal space with a glass micropipette (40- to 60-microns tip) to form a retinal bleb. Concentrations from 2.5 mg/L to 200 mg/L were well tolerated without ultrastructural toxic effects, while 1000 mg/L of human recombinant tissue-type plasminogen activator caused severe, irreversible toxic effects to the photoreceptor-retinal pigment epithelium complex. This toxic effect appeared to be due to the carrier vehicle rather than the human recombinant tissue-type plasminogen activator protein itself. Our results demonstrate that commercially prepared human recombinant tissue-type plasminogen activator can be safely used in the subretinal space of the cat with the range necessary for fibrinolysis.

Fibrin directs early retinal damage after experimental subretinal hemorrhage.

Subretinal blood within the macula may cause visual loss in a number of macular diseases. The clinical and histopathologic effects of experimental subretinal hemorrhage were evaluated in the cat. Subretinal hemorrhages were produced by creating a focal neurosensory retinal detachment with micropipette techniques, then inserting a needle tip transsclerally to allow choroidal blood to fill the bleb. Experimental lesions were examined clinically and with light and electron microscopy during a 14-day postoperative period. Initial observations included clot organization with retraction of fibrin strands. In six of nine clots more than 1 hour old, fibrin was associated with tearing of sheets of photoreceptor inner and outer segments. Later degeneration progressed to involve all retinal layers overlying the densest areas of fibrin in the clots. Hemorrhages into subretinal blebs containing tissue plasminogen activator did not form fibrin strands or cause photoreceptor tearing. These findings highlight the potential for improved retinal survival if organized subretinal clot can be eliminated soon after formation.

Treatment of retinopathy of prematurity with argon laser photocoagulation.

Fifteen eyes of nine infants were treated for retinopathy of prematurity by confluent photocoagulation of the avascular retina using an argon laser indirect ophthalmoscope. All treated eyes presented at or beyond threshold of stage 3 retinopathy of prematurity with "plus" disease. Three treated eyes had retinopathy of prematurity in zone I. Early complete regression of extraretinal proliferation was seen in 13 eyes. At 6 month's [corrected] minimum follow-up, 11 (73%) of the treated eyes demonstrated a favorable outcome, while four eyes (27%) progressed to an unfavorable outcome. No intraocular hemorrhages occurred during any laser treatment.

Atypical reginal vasculitis associated with ticlopidine hydrochloridine use.

PURPOSE: To describe two cases of retinal vasculitis shortly after the initiation of ticlopidine hydrochloride (Ticlid, Roche, Kingsland St, NJ) therapy. METHODS: Case reports of two patients. The first patient was a 43-year-old white woman complaining of spots, floaters, and flashes of lights in both eyes 3 weeks after the initiation of treatment with ticlopidine hydrochloride. The second patient was a 72-year-old woman complaining of decreased visual acuity in the left eye for 2 weeks, 4 weeks after initiating oral administration of ticlopidine hydrochloride. RESULTS: Both patients had resolution of the vasculitis after the discontinuation of ticlopidine therapy. CONCLUSION: The temporal relation and the resolution of symptoms after discontinuation of ticlopidine hydrochloride suggest that the vasculitis was related to the ticlopidine hydrochloride administration. Knowledge of this potential complication of ticlopidine hydrochloride is important for the early diagnosis of this possible drug-induced side effect and the cessation of ticlopidine hydrochloride.

High-dose intravenous pulse methylprednisolone hemisuccinate in acute Behçet retinitis.

PURPOSE: To report the response of acute Behçet retinitis to high-dose corticosteroids. METHOD: Case report. A 58-year-old man with Behçet disease and severe bilateral glaucoma experienced a sudden decrease of visual acuity to counting fingers in his (better-seeing) left eye. Examination disclosed hypopyon uveitis and an infiltrative retinitis threatening the fovea. He received intravenous methylprednisolone hemisuccinate, 1 gram per hour on each of 3 successive days, followed by oral prednisone and cyclosporine. RESULTS: The retinal infiltrate disappeared within 24 hours. Visual acuity improved to LE, 20/400 by day 5 and returned to LE, 20/30 after 3 months. A visual field demonstrated a scotoma corresponding to the location of the previous retinitis. CONCLUSION: High-dose intravenous methylprednisolone can reverse severe vision loss in acute Behçet retinitis.

Regression of cytomegalovirus retinitis associated with protease-inhibitor treatment in patients with AIDS.

PURPOSE: To report the observation that anti-retroviral therapy that includes a protease inhibitor can induce the regression of cytomegalovirus retinitis without requiring specific anticytomegalovirus drug therapy. METHODS: We examined the fundi of four patients with advanced acquired immunodeficiency syndrome (AIDS) who were placed on highly active antiretroviral therapy consisting of two nucleoside analogs and a protease inhibitor. The combined medications resulted in increased CD4+ T-lymphocyte counts and decreased load of human immunodeficiency virus (HIV-1). A prospective evaluation of the effect of these medications on an active cytomegalovirus retinitis lesion was conducted in one patient. Retinal lesions were documented with fundus photography. RESULTS: None of these patients received specific anticytomegalovirus medications. The average baseline CD4+ T-lymphocyte count was 33 cells per microliter (range, 4 to 88 cells per microliter) and increased an average of 118.5 cells per microliter (range, 66 to 185 cells per microliter). Average baseline plasma HIV-1 viral loads (HIV-1-RNA copies per ml) decreased 1.46 log units (range, 0.65 to 2.93 log units). In one patient, posterior progression (border advancement toward the posterior pole) of a cytomegalovirus retinitis lesion decelerated over time and stopped. Three other patients on initial examination had areas of retinal scarring consistent with healed cytomegalovirus retinitis. CONCLUSIONS: The addition of an HIV-1 protease inhibitor in the treatment of AIDS may lead to complete regression of cytomegalovirus retinitis without specific anticytomegalovirus medications. This effect may be related to reduced HIV-1 loads, a possible direct drug effect, an increase in CD4+ T-lymphocyte counts, or other associated changes in immune status.

Ultramicrosurgical removal of subretinal hemorrhage in cats.

Subretinal hemorrhages are associated with progressive degeneration of the outer retina and a corresponding poor visual prognosis. Mixed results have been reported in previous attempts to remove such subretinal hemorrhages. We developed an ultramicrosurgical system that used the control of a stereotactic micromanipulator to direct a micropipette tip through a small retinotomy into the subretinal space in three cat eyes. Low-dose recombinant tissue plasminogen activator was then introduced into the subretinal space around the subretinal hemorrhage via a controlled microinfusion system. The recombinant tissue plasminogen activator solution facilitated clot lysis and subsequent removal through the micropipette. Light- and electron-microscopic analysis of histopathologic specimens disclosed good preservation of retinal architecture in the three cat eyes in which experimental subretinal hemorrhages were removed. This was in contrast to the retinal degeneration observed in similar but untreated experimental subretinal hemorrhages.

Intraocular fluid cultures after primary pars plana vitrectomy.

To determine what organisms enter the eye and remain in the eye after pars plana vitrectomy, vitreous cavity aspirates were cultured postoperatively. Two of 33 (6%) consecutive eyes undergoing primary pars plana vitrectomy had positive cultures. One sample grew a single colony of Staphylococcus epidermidis, the second grew two colonies of Acinetobacter lwoffi. Neither of these eyes developed endophthalmitis. This study demonstrates that bacteria enter the eye at a low rate during pars plana vitrectomy and that the eye on which a vitrectomy has been performed is capable of clearing a low inoculum of bacteria.

Bartonella henselae infection associated with peripapillary angioma, branch retinal artery occlusion, and severe vision loss.

PURPOSE: To report atypical clinical features of Bartonella henselae neuroretinitis treated with combination antibiotics. METHOD: Case report. RESULTS: A 20-year-old man with a positive B. henselae titer developed a unilateral neuroretinitis, a large peripapillary angiomatous lesion, branch artery occlusion with ischemic maculopathy, and vision loss that failed to improve with clindamycin. Treatment with doxycycline and rifampin led to rapid clinical improvement. The severe vision loss in this case is atypical. CONCLUSIONS: Ocular findings associated with B. henselae infection may include retinal angiomatous lesion and branch retinal artery occlusion. Doxycycline and rifampin were successful in treating the infection.

The effect of silicone ocular surgical devices on serum IgG binding to silicones.

PURPOSE: To determine whether silicone materials used in retinal detachment repair and cataract surgery increase serum IgG binding to silicone and identify correlations with complications of ocular surgery. METHODS: Serum from 49 patients who had ocular surgery using silicone materials was examined. Patient groups included scleral buckling (n = 25), silicone oil tamponade (n = 3), scleral buckling and silicone oil tamponade (n = 9), and silicone lens implants after cataract extraction (n = 12). Convalescent samples for all patients and preoperative samples from 19 patients (18 scleral buckling and one silicone oil tamponade) were examined. Postoperative complications were monitored for up to 108 months (mean, 10.7 months; mode, 1.5 months; range, 1 to 108 months). Samples were evaluated for the extent of IgG binding to silicones using a micromodification of a previously described enzyme-linked immunosorbent assay method. RESULTS: In 19 patients, IgG binding levels in preoperative samples were 21 arbitrary units (AU) or less. Of the 25 buckling patients, one developed complications; however, in all patients the postoperative levels of IgG binding to silicone were low (2.2 to 20.0 AU). Although four silicone lens patients developed mild complications, none displayed postoperative IgG binding levels of greater than 20 AU. Three patients who underwent both scleral buckling and silicone oil tamponade developed complications; one of these patients, who was also noted to have systemic connective tissue disease, had a significant elevation in postoperative serum IgG binding to silicone. CONCLUSIONS: Statistically significant elevations of serum IgG binding to silicone were noted postoperatively in only one patient who had a systemic connective tissue disease. The complication rate and frequency of enhanced serum IgG binding to silicone was low, making correlations to surgical complications difficult. Examination of matched samples suggested that if ocular exposure to silicone implants enhances the level of serum IgG binding to silicones, it must be a rare event that should not alter the clinical use of these important devices.

Corneal perforation associated with argon laser photocoagulation for a retinal tear.

PURPOSE: To report a corneal perforation during argon laser photocoagulation around a retinal tear following pneumatic retinopexy. METHODS: The patient was examined and found to have a corneal perforation with pigment in the base of the wound. To help explain this phenomenon, we evaluated the ability of argon blue-green laser to create a corneal perforation in a cadaver eye. RESULTS: In a cadaver eye, we induced a corneal perforation with argon laser only when a pigmented substance was present on the corneal surface. CONCLUSIONS: We hypothesize that pigmented material such as an eyelash or mascara caught between the cornea and contact lens interface may have facilitated this rare complication. Clinicians should be wary of any pigmented substance on the surface of the cornea or ophthalmoscopic lens when performing argon laser photocoagulation.

Vascular endothelial growth factor and fibroblast growth factor 5 are colocalized in vascular and avascular epiretinal membranes.

PURPOSE: To determine by immunocytochemical analysis of epiretinal membranes whether vascular endothelial growth factor and the fibroblast growth factor FGF-5 are present in patients with proliferative diabetic retinopathy or proliferative vitreoretinopathy. METHODS: Human surgical specimens of epiretinal membranes were obtained from 11 eyes with proliferative diabetic retinopathy and five eyes with proliferative vitreoretinopathy. Sections were immunostained with an affinity-purified antibody against an internal sequence of human FGF-5 and with a commercially available affinity-purified antibody corresponding to the first 20 residues of human vascular endothelial growth factor. Slides were visualized using avidin-biotin-peroxidase complex. Control studies were performed with nonimmune immunoglobulin G and preabsorbed vascular endothelial growth factor and FGF-5 antibody, respectively. RESULTS: Immunoreactive FGF-5 is present in most cells, including endothelial cells of vascular and avascular epiretinal membranes, but seems to be absent from the extracellular matrix. A similar staining pattern was observed for vascular endothelial growth factor. CONCLUSIONS: Vascular endothelial growth factor and FGF-5 are remarkably colocalized in both vascular and avascular epiretinal membranes arising from proliferative diabetic retinopathy and proliferative vitreoretinopathy, respectively. This result questions the concept that the presence of a single angiogenic factor determines the vascular status of an epiretinal proliferation.

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.