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RD is a serious and well-known complication after cataract surgery, developing in 1% to 3% of all patients undergoing cataract extraction. High myopia, disruption of the posterior capsule intraoperatively or postoperatively by Nd: YAG laser, and vitreous loss increases the risk for RD. Retinal evaluation with detailed indirect ophthalmoscopy with scleral indentation and prophylactic treatment to all lesions that contribute to retinal tear and RD is strongly advocated before cataract surgery and Nd: YAG laser capsulotomy. Intraoperative vitreous loss should be managed meticulously, and these patients should be examined more frequently in the postoperative period. During phacoemulsification, no attempts should be made to retrieve the dislocated nuclear fragments without proper vitrectomy. It is best advised that a vitreoretinal surgeon handles the complication. Early recognition and prompt treatment following the detachment can result in good visual recovery.

Whipple's disease is a multisystem bacterial disease usually characterized by malabsorption, diarrhea, and polyarthritis. Ocular manifestations of Whipple's disease include blurred vision or visual loss with one or more of the following findings: vitritis, uveitis, retinitis, retinal hemorrhage, choroiditis, papilledema, optic atrophy, and keratitis.1 In general, these ocular manifestations occur in patients who also have gastrointestinal or central nervous system involvement. We report a case of chronic, bilateral uveitis with unusual ophthalmologic features. The patient had no clinical evidence of gastrointestinal disease, and light microscopy of repeated duodenal-biopsy specimens was negative. A preliminary diagnosis of Whipple's disease was made on . . .

An enhanced understanding of the microcirculation and blood flow in glaucoma is needed. Definitive study has been impaired by lack of a quantitative and objective clinical method to measure human optic nerve and peripapillary choroidal blood flow. Through optical sectioning of the optic nerve head and peripapillary retina, confocal scanning laser ophthalmoscopy offers the potential for angiographic examination of small vessels, particularly at the level of the lamina cribrosa.

■ Diagnostic vitreoretinal surgery should be considered when other noninvasive methods of diagnosis have failed to establish a pathoetiologic mechanism. ■ The goals of ocular biopsy should be to acquire microbiological, cytologic, histologic, immunologic and genetic information, with minimum surgical trauma, for modifying and directing medical and surgical treatments. ■ The development of a 25-gauge operating system introduces a new concept in vitreous, retinal and choroidal biopsy. ■ Vitreous, retinal or choroidal biopsy are relatively safe procedures, and the results often change clinical management. ■ 25-gauge procedures induce minimal ocular trauma, decrease the inflammatory response, and may allow faster overall patient recovery.

The post-irradiation regression rate of uveal melanomas is a prognostically significant factor for the development of metastases. Other predictive factors for metastases are histological networks which are imagable with confocal ICG angiography. The purpose of this study was to evaluate a possible connection of networks in the ICGA and tumor regression rates.We compared the post-irradiation regression rates (as %) in 20 patients 1 year after brachytherapy with networks identified in pre-treatment indocyanine green angiography (ICGA). The ICG angiography was performed before irradiation, 10 patients were irradiated with Ru-106 and 10 were irradiated with Id-125.The mean preoperative maximum apical height was 5.2 mm [SD: 1.5 mm; Ru106 group: 5.7 mm (SD: 1.0 mm); Id-125 group: 5.0 mm (SD: 1.9 mm)]. In 11 patients (55%) (Ru-106: 5; Id-125: 6) we found networks in the preoperative ICG. The mean regression rate in tumors with networks was 51.3% (SD: 14.7%) and 28.0% (SD: 16.4%) in the group without networks. The difference between both groups was statistically significant (p = 0.003, Mann-Whitney test). No statistically significant difference in the regression rates was found between the two groups of brachytherapy Ru-106 and Id-125 (p = 0.165, Mann-Whitney test).Highly proliferative tumors are known to be more sensitive to irradiation. This may be one reason why tumors with a rapid post-irradiation regression are the more aggressive ones with regard to later development of metastases. Histopathological networks are also known to be a strong indication of more aggressive, metastasizing tumors. These networks are also imagable in ICG angiography. Our observation emphasizes a connection between networks in ICG angiography and regression rates of uveal melanomas after brachytherapy.

Histologically demonstrable microcirculation patterns (microcirculation pattern) of human choroidal melanomas have prognostic significance for the patient. We report on our experience in imaging these microcirculation pattern in vivo using simultaneous confocal Fluorescein (FA)- and Indocyaninegreen (ICG) angiography before and after brachytherapy.The simultaneously procured confocal FA- and ICG angiograms of 50 patients with untreated choroidal melanomas were studied for the visibility of microcirculation pattern. Patients were also followed with simultaneous FA/ICG after brachytherapy.Confocal FA disclosed signs of tumor vascularization in 12 (24%) of the 50 examined patients but microcirculation pattern only in 3 patients (6%). In contrast, simultaneously obtained confocal ICG disclosed microcirculation pattern in 47 patients (94%). In 10 (77%) of the 13 patients the tumor microcirculation changed considerably after brachytherapy: Distortion, thickening, thinning, as well as complete obliteration of vessels could be observed.Histologically demonstrated microcirculation pattern can be imaged in vivo. This offers the possibility to assess the likely biologic behavior of the individual tumor without the need for obtaining a cytologic or histologic specimen via enucleation or fine-needle biopsy. Confocal ICG angiogiography images microcirculation pattern better than FA which can be explained by the different absorption-, fluorescence- and exudation-characteristics ICG. Follow-up with confocal ICG of choroidal melanomas after brachytherapy shows different features and allows for visualization of the microcirculation reaction to the treatment which might be a useful tool for studying the effects of future anti-angiogenesis based tumor therapies.

We have previously shown that histologically described microcirculation patterns (MCP) can be visualized with indocyanine green (ICG) angiography. We have designed a prospective study to evaluate the prognostic value of these angiographically imaged MCP in small choroidal melanocytic lesions. In this report we describe the design of the study, characterize the patient collective, and present the first results.In this prospective nonrandomized observational study, unilateral choroidal melanocytic lesions with 1.5-5.5 mm maximum apical height are observed until growth is determined according to defined criteria. Variables are demographic parameters, subjective symptoms, subretinal fluid, location and dimension of tumor, hemorrhage, color, orange pigment, and MCP determined by ICG angiography: normal, straight, parallel without crosslinking, parallel with crosslinking, arcs without branching, arcs with branching, loop, and network.Seventy patients (22 males, 48 females; age: 33-88 years, median: 64 years) have been included up to now: 19 tumors showed growth so far (time to growth: 51-946 days, median: 127 days). The following parameters were statistically significantly correlated with time to tumor growth: flashes (p = 0.082), orange pigment (p = 0.012), subretinal fluid (p0.001), maximum basal tumor diameter (p = 0.001), maximum apical tumor height (p0.001), parallel with crosslinking (p0.001), arcs with branching (p = 0.006), loop (p0.001), and network (p0.001). Of these, complex MCP (parallel with crosslinking, arcs with branching, loop and/or network) showed the strongest correlation with time to tumor growth in a Cox regression model. Based on our data, the positive predictive value of imaging complex MCP (for growth within 12 months) is 78% and the negative predictive value is 98%.Our patient collective demonstrates comparable prognostic parameters for time to growth as described in the literature. In addition, the ICG angiographic detection of complex MCP is more strongly predictive of the time to growth than other clinically determinable factors. Thus, we recommend this examination for patients with small choroidal melanocytic lesions, if the patient is to be counseled regarding the likely biologic behavior of his tumor.

To report the association between duration of vitrectomy, as well as other risk factors, and the progression of nuclear sclerosis and posterior subcapsular cataract in the Vitrectomy for Macular Hole Study.A cohort study nested within a randomized controlled clinical trial.Using a system similar to the Lens Opacities Classification System II, nuclear sclerosis (NS) and posterior subcapsular cataract (PSC) were scored in the vitrectomy and fellow eye of 74 patients at baseline and at 6, 12, and 24 months postoperatively. Age, baseline blood pressure and refractive power, and duration of surgery were evaluated as risk factors for NS or PSC progression and cataract extraction.The incidence of NS progression in the surgical group of vitrectomy eyes was 81% at 6 months, 98% at 1 year, and 100% at 2 years of follow-up. In contrast, NS progression in the control group of fellow eyes was only 18% at 6 months, 20% at 1 year, and 8% at 2 years. The incidence of PSC progression in the surgical group remained at approximately 11% throughout follow-up, which was not significantly higher than the 3% to 5% incidence in the control group. Vitrectomy was significantly related to progression of NS cataract (P.001) and cataract extraction (P.01). No statistically significant differences were found for NS scores, PSC scores, or progression rates between eyes that had less than median surgical duration (60 min.) or more than the median surgical duration. Additionally, no significant differences were found when eyes that experienced 45 minutes or less surgical duration were compared with eyes that endured more than 75 minutes surgical duration. Age, blood pressure, and refractive power were not found to be predictors for NS and PSC progression.Although vitrectomy is a risk factor for NS progression, the duration of vitrectomy does not increase the risk.

To report on the prevalence, correlates, and natural history of epiretinal membranes (ERM) in eyes with stage II or III/IV macular holes.A subgroup analysis arising from a multicentered, controlled, randomized clinical trial.Community and university-based ophthalmology clinics.Two hundred twenty four eyes with stage II or III/IV macular holes.No intervention for 100 eyes randomly assigned to observation.Grade of ERM determined by stereoscopic examination of fundus photographs at baseline and at 3, 6, 12, and 24 months of follow-up.The prevalence of ERM was 65% (145 of 224 eyes), was greater in pseudophakic than in phakic eyes (80% vs. 63%, P = 0.10), and increased with increasing severity of the hole (P0.0001). Stage III/IV eyes with ERM had a significantly larger hole size than did eyes without ERM (P0.01); however, no association between presence of ERM and visual acuity was found (P0.5). In the 100 phakic eyes that were randomly assigned to observation, there was a significant increase in the severity of ERM over follow-up (P0.0001).ERM are common in eyes with full-thickness idiopathic macular holes. Although ERM prevalence increases with severity and size of the macular hole, the presence of ERM are not closely correlated with visual acuity. These factors may be important in considering the removal of ERM during vitrectomy for macular hole.

To characterize cytomegalovirus (CMV) retinitis in human immunodeficiency virus (HIV)-infected patients who demonstrate immune recovery while receiving highly active antiretroviral therapy (HAART).Consecutive, noncomparative case series.Twenty-two HIV-positive patients, from two institutions, with a history of CMV retinitis, and with elevated CD4 cell counts after HAART.Duration of healed CMV retinitis without anti-CMV therapy, CD4 cell count, and HIV viral load.Discontinuation of anti-CMV therapy after persistent elevation of CD4 cell count over 50 cell/mm3 (median, 161/mm3; range, 85-408/mm3).The median period of healed CMV retinitis without anti-CMV therapy was 72 weeks (range, 33-116 weeks). Nineteen of 22 patients were still healed without anti-CMV therapy at study end. The three patients with CMV retinitis progression simultaneously had HAART, fail with CD4 cell counts of 37, 35, and 47/mm3.HIV-positive patients with CMV retinitis, who demonstrate a sustained HAART-induced elevation of CD4 cell count on two consecutive counts 3 months apart and whose retinitis remains healed on anti-CMV therapy for greater than 4 months, are likely to remain healed if the anti-CMV therapy is withdrawn. It is important to monitor these patients with indirect ophthalmoscopy because HAART failure may occur and allow CMV retinitis reactivation.

To evaluate the intraocular safety and antiviral treatment efficacy of the sustained lipid prodrug of ganciclovir, 1-O-hexadecylpropanediol-3-phospho-ganciclovir (HDP-P-GCV), as an intravitreal injectable drug system for viral retinitis.HDP-P-GCV was synthesized by coupling 1-O-hexadecyl-propanediol-3-phosphate to either free hydroxyl of ganciclovir in pyridine with dicyclohexylcarbodiimide as catalyst. The compound was formulated into liposomes. The antiviral activity was assessed by DNA reduction in vitro, and intraocular safety was assessed by ophthalmoscopy, electrophysiology, and histology after intravitreal injections, with resultant intravitreal concentrations of 0.2, 0.632, 1.12, and 2 mM. The treatment efficacy was evaluated by simultaneous intravitreal injection of HDP-P-GCV and herpes simplex virus type 1 (HSV-1) or by intravitreal injection of HDP-P-GCV at various times before HSV-1 intravitreal inoculation. Retinitis was scored with ophthalmoscopy and compared with controls.In vitro, the IC50 of HDP-P-GCV against HSV-1 and human cytomegalovirus (HCMV) infected cells was 0.02 and 0.6 microM, respectively. In rabbits in vivo, HDP-P-GCV dispersed evenly and maintained a good vitreous clarity at all doses except 2 mM final intravitreal concentration. Although cataracts were observed in some eyes at the higher doses, they were not observed in eyes with 0.2 mM final intravitreal concentration. No other indications of ocular toxicity were observed. Intravitreal injection of HDP-P-GCV with resultant 0.2 mM intravitreal concentration in the HSV-1 retinitis rabbit model demonstrated a complete protection of the retina with the simultaneous treatment strategy and a 4 (P = 0.03) to 6-(P = 0.058) week significant protection of retina with the pretreatment strategies when compared with ganciclovir or blank liposome controls.In the rabbit model of HSV-1 retinitis HDP-P-GCV acts as a long-lasting intravitreal injectable anti-CMV or anti-HSV compound. This self-assembling liposome system could be applicable for many compounds available for intraocular diseases.

To delineate the immune parameters associated with reactivation of cytomegalovirus (CMV) retinitis in patients for whom highly active antiretroviral therapy (HAART) was not successful.Prospective, longitudinal observational study of a cohort of 102 patients with CMV retinitis treated with HAART and being followed up at the AIDS Ocular Research Unit of the University of California, San Diego from November 1995 to November 1998. The study included serial clinical and fundus photographic examinations with CD4 T-lymphocyte counts and HIV viral load measurements.Forty-seven of the 102 patients with CMV retinitis responded to HAART. Thirty-five of the patients were successfully withdrawn from anti-CMV therapy. During a median follow-up of 74.71 weeks (range, 4.86-144 weeks) after discontinuation of anti-CMV therapy, four patients experienced a reactivation of CMV retinitis. In each case, the CD4 count decreased before reactivation to a median of 31.5 cells/mm3 (mean, 31.25 cells/mm3; range, 23-39 cells/mm3). The association between the CD4 count decreasing to less than 50 cells/mm3 and reactivation of CMV retinitis was statistically significant (P0.0003).Four patients treated with HAART experienced reactivation of CMV retinitis as their CD4 count decreased. The threshold CD4 count below which reactivation of CMV retinitis occurred in patients for whom HAART was not successful appeared to be 50 cells/mm3. Despite an initial response to HAART, patients are still at risk for reactivation of CMV retinitis if their CD4 count decreases to less than 50 cells/mm3. The HIV viral load did not appear to predict CMV reactivation.

To evaluate and compare the risks and benefits of autologous serum as an adjuvant therapy in macular hole surgery for stage 3 or 4 macular holes.Comparison of 2 consecutive (nonrandomized) cohorts using standardized methods for the determination of hole size and for surgical procedures, and using the same study surgeons. The serum cohort consisted of 106 eyes using autologous serum as an adjuvant, and the no serum cohort consisted of 58 eyes without adjuvants. The primary end point was the closure of the macular hole as determined by the 6-month fundus photographs. Secondary end points included the number and types of postoperative complications. Comparison in outcomes between the 2 cohorts used chi2 and logistic regression procedures, adjusting for preoperative differences between the study cohorts.At 6 months, the (unadjusted) rate of hole closure was significantly greater for the eyes treated with serum than for the eyes not treated with serum (90 [85%] of 106 vs. 40 [69%] of 58, P = .04). However, after adjusting for preoperative differences in hole diameter and the prevalence of epiretinal membranes, no overall difference in hole closure rates due to serum was found (P = .44). In contrast, benefit due to serum for large holes (diameter573 microm) was seen (12 [75%] of 16 vs 13 [57%] of 23, P = .04). No differences in complication rates were found between the cohorts.Any beneficial effect of serum used as an adjuvant to macular hole surgery is small, and, if present, the beneficial effect may be limited to larger holes. A randomized, prospective, controlled study in larger macular holes is needed.

This study was conducted to evaluate the vitreous clarity and intraocular therapeutic index of three preparations ofthe carboxymethyl ester of 1-O-octadecyl-sn-glycerol-3-phosphonoformate (ODG-PFA-O-Me), a long acting lipid derivative of foscarnet with potent anti-CMV activity. Twenty-six New Zealand white rabbits were intravitreally injected with one of three preparations of ODG-PFA-O-Me or control diluent. The vitreous clarity was graded after injection using indirect ophthalmoscopy and fundus photography. Drug intraocular toxicity was evaluated by electroretinography and by post-sacrifice tissue pathology using light and electron microscopy. Intravitreal injection of micellar ODG-PFA-O-Me showed variable local retinal toxicity and vitreal compound aggregates in eyes with the middle and high doses. The intraocular therapeutic index was lower than 465:1. Intravitreal injection of liposomal ODG-PFA-O-Me, either free acid or sodium salt, revealed clear vitreous for the 0.632 and 0.84 mM final intravitreal concentrations. No retinal toxicity was confirmed for the 1.12 mM final intravitreal concentration at the eight week observation following injection. The intraocular therapeutic index was between 585-1037:1. ODG-PFA-O-Me possesses better vitreous compatibility than ODG-PFA. Liposomal ODG-PFA-O-Me can be intravitreally injected with a resulting clear vitreous and high intraocular therapeutic index. Liposomal ODG-PFA-O-Me could be a long acting nontoxic intravitreous injectable drug for CMV retinitis.

To determine intraocular toxicity and efficacy of the lipid prodrug of foscarnet, 1-O-octadecyl-sn-glycerol-3-phosphonoformate (ODG-PFA), as a long-acting, nontoxic intravitreous injectable drug delivery system for cytomegalovirus (CMV) retinitis.ODG-PFA was synthesized by coupling the phosphonate residue of PFA to the 3 hydroxyl of 1-O-octadecyl-sn-glycerol and formulated as micelles and liposomes at concentrations so that, after injection into the rabbit vitreous, the resultant intravitreal concentrations were 0.2 mM, 0.63 mM, and 2 mM in micellar formulation and 0.02 mM, 0.063 mM, 0.2 mM, and 0.63 mM for liposomal formulation. The compounds were injected, and toxicology evaluations were performed.Intravitreal injections of micellar ODG-PFA resulted in aggregation of the material in vitreous and variable local retinal damage. Intravitreal injections of the liposomal ODG-PFA revealed even dispersion of the compounds and a clear vitreous, using final concentration in the vitreous of 0.2 mM. No intraocular toxicity was found with the 0.632 mM final concentration. The 50% inhibitory concentration (IC50) for CMV of ODG-PFA was 0.43+/-0.27 microM, and the therapeutic index of ODG-PFA after intravitreal injection was estimated to be 1470:1.Lipid-derivatized foscarnet liposome formulations may be a useful long-acting delivery system for the therapy of CMV retinitis.

To examine the relationship between loss in peripheral visual sensitivity and neuropsychological functioning in seropositive patients with human immunodeficiency virus (HIV) without infectious retinopathy.Subjects carefully screened for retinal disease and well-matched across demographic and medical variables were grouped according to normal (perimetry-nl) versus abnormal (perimetry-abnl) performance on achromatic automated perimetry and short-wavelength automated perimetry, standard clinical ophthalmologic measures of visual function. All subjects completed a detailed neuropsychological test battery and were classified as impaired or unimpaired, globally and across eight neurocognitive domains. Subjects were also classified according to whether they met diagnostic criteria for minor cognitive/motor disorder (MCMD) or HIV-associated dementia (HAD).Visual field loss was associated with lower performance in the abstraction, perceptual-motor, learning, and motor domains. Significant group differences were also found on numerous individual neuropsychological tests. Based on clinical ratings, we found deficits in learning and motor functioning. No perimetry-nl subjects met criteria for MCMD or HAD, whereas 32% of perimetry-abnl subjects met diagnostic criteria for syndromic cognitive disorders (five MCMD and one HAD). In a subset of subjects who underwent a lumbar puncture, there was a trend for the perimetry-abnl group to have a higher concentration of beta2 microglobulin, a marker for central nervous system immune activation.These results suggest that in some HIV-infected people reduced visual function may be caused by nonretinal disease, and perimetry may present a sensitive measure of HIV-related brain dysfunction.

To study the course and visual outcome of Vogt-Koyanagi-Harada (VKH) syndrome in children.The medical records of 97 consecutive patients with VKH syndrome were reviewed. Patients had been seen at King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia. The records were divided into two groups: those in whom the onset of the disease occurred at the age of 14 years or younger (pediatric group) and those in whom the disease manifested after the age of 14 years (adult group).Eight (61%) of the 13 children required cataract surgery compared to 14(17%) of 84 adult patients. Despite medical and surgical therapy, eight (61%) of the pediatric group had a final visual acuity of 20/200 or worse compared with 22 (26%) of the 84 adult patients (p=0.0103).The course of early-onset VKH (before the age of 14 years) appears to be aggressive. The ocular complications are more severe in children than in adults, leading to rapid deterioration in vision. Despite therapy, the final visual outcome of VKH in children is poor.

We describe a case of focal cytomegalovirus iritis in a patient with acquired immunodeficiency syndrome (AIDS) who had CMV retinitis. The autopsy showed histologic evidence of focal iritis in the left eye. This iritis was characterized by infiltration of acute inflammatory cells mixed with cytomegalic cells, which was confirmed by CMV-specific immunohistochemical staining. The case suggested that cytomegalovirus could be a direct causative agent of infectious iritis in AIDS patients.

To determine capillary blood flow measurements in eyes with branch retinal vein occlusion using a scanning laser Doppler flowmeter.Retinal capillary blood flow in branch retinal vein occlusion areas and corresponding ipsilateral nonbranch retinal vein occlusion areas, 11 equivalent areas of the contralateral fellow eye of 12 consecutive untreated branch retinal vein occlusion patients, and 16 eyes of 11 age-matched normal control subjects were measured with scanning laser Doppler flowmetry. A template consisting of eight squares, each with a field of 100 x 100 microm (10 x 10 pixel) with space interval of 500 microm equidistant horizontally and vertically was used to obtain blood flow measurements in all subjects. Mean blood volume, flow, and velocity were obtained by averaging the mean values measured in each field. We avoided measurement over large retinal vessels to prevent the aliasing artifact of blood cells from moving faster than the sampling frequency.Branch retinal vein occlusion areas have significantly decreased microvascular blood volume (P = .0009), flow (P = .02), and velocity (P = .016) compared with ipsilateral nonbranch retinal vein occlusion areas in the same eye. Branch retinal vein occlusion areas also have decreased blood volume (P = .001), flow (P = .0042), and velocity (P = .0044) compared with areas of contralateral fellow eyes of branch retinal vein occlusion subjects. Branch retinal vein occlusion areas have significantly decreased blood volume (P = .0012), flow (P = .008), and velocity (P = .02) compared with age-matched normal areas.Average retinal blood volume, flow, and velocity in areas of branch retinal vein occlusion are significantly lower than in healthy retinas. The ability to noninvasively measure hemodynamic changes in the retinal capillary bed may be relevant to development of new therapies for retinovascular disease.

The authors prospectively studied visual outcome, relapse, complications, and survival of patients with acquired immune deficiency syndrome (AIDS)-related cytomegalovirus (CMV) treated with high-dose intravitreous ganciclovir (2 mg/0.1 ml) injections. The outcomes were compared with those of patients treated with standard doses of intravenous ganciclovir in the same institution. The histopathologic and electrophysiologic effects of high-dose intravitreous ganciclovir injections in rabbits also were studied.A nonrandomized case series.A total of 42 patients (74 eyes) were treated with intravitreous injections and 18 patients (27 eyes) were treated with intravenous ganciclovir. Five eyes of three New Zealand white rabbits were injected with ganciclovir, and the sixth eye was a control specimen.Patients treated with intravitreous injections received twice-weekly doses of 2 mg/0.1 ml ganciclovir for 3 weeks, then weekly injections. Patients treated with intravenous ganciclovir received standard doses. Patients were monitored with regular examinations. Rabbit eyes were given intravitreous injections of 1 mg/0.1 ml of ganciclovir weekly for 4 weeks.Assessments of vision, retinal inflammation, and survival were made. Electroretinograms were performed on the rabbit eyes, and they were processed for light and electron microscopy.In the intravitreous group, visual acuity (VA) was stable in 64 of 74 eyes, 5 improved, and 5 deteriorated. Sixty-three (85%) of 74 eyes had final VA of 20/20 to 20/40. Relapse occurred in five eyes (7%; median time, 42 weeks). There were three cases of endophthalmitis. Median survival after diagnosis of CMV retinitis was 36 weeks. In the intravenous group, VA was stable in 18 eyes, 0 improved, and 9 deteriorated. Sixteen (59%) of 27 eyes had final VA of 20/20 to 20/40. Relapse occurred in 15 eyes (56%) at a median time of 21 weeks. Median survival was 21 weeks. The rabbit studies showed no evidence of toxicity.High-dose intravitreous ganciclovir effectively suppressed CMV retinitis, preserved vision, and prevented relapse without deterioration in survival.

To characterize the anterior segment effects of cidofovir, using an animal model.Cidofovir drops, at concentrations of 0.04%, 0.4% and 4%, were instilled in eyes of guinea pigs once daily for 10 days. Fellow eyes (controls) received normal saline. The corneal epithelium was debrided at day one and then at every other day for 10 days. Subconjunctival injections of 20 microl of 4% cidofovir were given in another group of animals. A micromanometer was used to determine the intraocular pressure (IOP). Eyes were studied histopathologically at the conclusion of the study.There was no significant drop in IOP after 10 days, using the 0.04% concentration of cidofovir drops. Histology revealed mild corneal edema and inflammatory infiltrate; iris, ciliary body and retina were normal. There was a statistically significant drop in IOP in the eyes treated with 0.4% and 4.0% cidofovir eye drops at 10 days (p = 0.005 and p0.0001, respectively) compared to baseline. Morphological changes included moderate to severe corneal edema, vascularization and inflammatory infiltration. The iris and ciliary body revealed mild inflammatory changes only at the 4% cidofovir dose. No changes were seen in the retina with any doses. No change in IOP was observed following subconjunctival injections of 4% cidofovir, and histologically, only localized inflammatory changes in the conjunctiva were observed.The IOP-decreasing effect of cidofovir occurs at doses below those causing intraocular inflammation and is likely due to an effect on the anterior segment. The anterior segment effects of cidofovir in guinea pigs were similar to those in humans. Thus, the guinea pig appears to be a good animal model for studying the effects of cidofovir on the anterior segment structures.

Cidofovir (HPMPC) is a potent long-acting anticytomegalovirus agent. In humans, its dose-limiting intravitreal toxicity results in the lowering of intraocular pressure (IOP). The purpose of the present study was to determine the effects of HPMPC and various acyclic nucleoside phosphonate (ANP) analogues when administered intravitreally in guinea pig eyes and to establish the structural and functional relation of these compounds in connection with their effects on the ciliary body and retina.Ninety-six guinea pig eyes were injected with various doses of HPMPC and ANP analogues.Severe lowering of IOP with structural alterations of the ciliary body was observed when doses were administered that achieved final intravitreal concentrations greater than 25 microg/ml HPMPC, 200 microg/ml cyclic HPMPC (cHPMPC), 25 microg/ml (S)-HPMPA, and 625 microg/ml PMEG. Concentrations of 25 microg/ml HPMPC, 200 microg/ml cHPMPC or less, and all concentrations of (R)-HPMPA, HPMPU, PMEA, PMEC, PMEDAP, (R)-PMPA, and (S)-PMPA did not lower IOP significantly, nor did they cause significant histologic changes.Of the HPMP series, the cyclic analogue of HPMPC (cHPMPC) and HPMPC are the least toxic of the compounds that show potent anti-human cytomegalovirus activity (HCMV). PMEG, the most potent anti-HCMV compound of the PME series, is toxic at higher doses. Further evaluation of lower doses is needed. Compounds of the PMP series are not toxic, but they show no anti-HCMV activities. The IOP-lowering effect of these compounds appears to be associated with an effect on the ciliary body.

To study complications of vitrectomy surgery for full-thickness macular holes.A multicentered, randomized, controlled clinical trial.Community and university-based ophthalmology clinics.Standardized macular hole surgery versus observation.Assessment of anatomic and visual outcomes and determination of postoperative complications at 12 months after randomization.Posterior segment complications were noted in 39 eyes (41%). The incidence of retinal pigment epithelium (RPE) alteration and retinal detachment (RD) were 33% and 11%, respectively. One RD due to a giant retinal tear resulted in a visual acuity of light perception. Other complications included a reopening of the macular hole in 2 eyes (2%), cystoid macular edema in 1 eye (1%), a choroidal neovascular membrane in 1 eye (1%) and endophthalmitis in 1 eye (1%). Eyes with complications had significantly worse visual acuity outcomes as determined by the Early Treatment Diabetic Retinopathy Study, Word Reading, and Potential Acuity Meter charts (P0.01 for all comparisons). Eyes with macular holes greater than 475 microns were more than twice as likely to have complications than eyes with holes less than 475 microns (odds ratio [OR] = 2.2, P = 0.07). Before surgery, the stage of the hole was related to postoperative RPE changes (P0.0001) and the occurrence of postoperative RD (P = 0.0002). Intraoperative trauma was related to the occurrence of these complications (P0.0001 for RPE changes, P = 0.02 for RDs). Epiretinal membrane removal was related to RPE changes (P = 0.02) but not RDs.The RPE alterations and RDs are common after macular hole surgery and result in significantly reduced postoperative visual acuity. The RPE changes may be related to surgical trauma or light toxicity. Further efforts to reduce complications associated with macular hole surgery are indicated.

Rifabutin-related uveitis has been reported in AIDS patients who take a daily dose of 300 to 1800 mg of this drug. Presumed rifabutin-related uveitis is characterized by unilateral or bilateral anterior chamber inflammation with hypopyon accompanied by hyperemia, pain, photophobia, and vitritis. However, retinal manifestations or vitreous cytology of this entity have never been reported. This report describes a patient who had retinal vascular changes associated with uveitis while being treated with oral rifabutin. Fundus photographs and fluorescein angiograms documented resolved retinal vasculitis. Vitreous cytology of this case showed acute inflammatory cells. To the authors' knowledge, this is the first report of retinal vasculopathy in a patient with rifabutin-related uveitis and the first analysis of the vitreous cytologic aspects of this disease.

The authors characterize and analyze the incidence of a previously reported mild anterior nongranulomatous uveitis associated with intravitreal injections of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), also termed cidofovir (Vistide, Gilead Sciences, Foster City, CA). This is an acyclic nucleoside phosphonate analogue with a potent anticytomegalovirus effect. The authors also analyzed the effects of probenecid therapy, as well as prophylaxis with probenecid plus topical corticosteroids and cycloplegics on the course and outcome of the uveitis.Prospective case series from a tertiary referral center, which included 46 consecutive patients with acquired immune deficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis. There was a total of 130 injections in 69 eyes treated with 20 micrograms of intravitreal HPMPC. Forty-one patients (119 injections) received oral probenecid, 5 patients (11 injections) did not, and 21 patients (53 injections) received topical corticosteroids and cycloplegics as an adjuvant to probenecid in the prophylaxis of iritis.Mild to moderate nongranulomatous iritis was seen in 26% of patients after their first injection (n = 12). Patients receiving probenecid prophylaxis after first injection had a significantly lower frequency of iritis versus patients who did not receive probenecid at the time of first injection (P = 0.0089). In contrast, treatment with topical corticosteroid and cycloplegics after injection did not statistically significantly affect the frequency of iritis in patients (P = 0.44). The development of iritis after a second injection of HPMPC was more likely if it had occurred after the initial injection (P = 0.015; Fisher's exact test). All cases of iritis were treated with topical corticosteroids and cycloplegics, and there was no permanent impairment of vision secondary to iritis after HPMPC injection in any eyes.Anterior uveitis was seen in 26% of patients after first-time HPMPC injection. Concomitant use of probenecid appears to decrease the frequency of the iritis from 71% to 18% in patients with AIDS and CMV retinitis after the first intravitreal injection of HPMPC. Topical corticosteroid administration after injection (before iritis) was ineffective in preventing iritis treatment with topical corticosteroids and cycloplegics resulted in resolution of all iritis cases.

To prospectively assess the risks and benefits of vitrectomy surgery for eyes with stage 3 or 4 macular holes.A multicentered, controlled, randomized clinical trial.Community- and university-based ophthalmology clinics.One hundred twenty patients (129 eyes) with stage 3 or 4 macular holes.Standardized macular hole surgery vs observation alone.Four measures of best-corrected visual function, standardized photographic evaluation of the extent of hole closure, evaluation of lens opacification, and determination of adverse events. Outcomes were determined at 6 months after randomization.Compared with observation alone, a significant benefit due to surgery was found in the rate of hole closure (4% vs 69%, P.001). After adjusting for baseline visual acuity, hole duration, and maximum hole diameter, a significant benefit due to surgery was found in visual acuity for the Bailey-Lovie Word Reading (P = .02) and the Potential Acuity Meter (P.01) tests; a marginally significant benefit due to surgery was found in visual acuity for the Early Treatment Diabetic Retinopathy Study chart (P = .05). Although the proportion of eyes achieving a change in visual acuity of 2 or more lines on the Early Treatment Diabetic Retinopathy Study chart was significantly greater for the surgery group vs the observed group (11 [19%] of 59 eyes vs 3 [5%] of 58 eyes, adjusted P = .05), 20 (34%) of 59 eyes randomized to surgery had a loss in visual acuity of 1 or more lines. Compared with the observation group, eyes randomized to surgery had higher nuclear sclerosis scores (2.4 vs 1.3, P.001). Fourteen adverse events were noted in the surgery group; none were noted in the observed group.Some visual benefit of vitrectomy surgery for macular holes exists, despite a notable incidence of adverse events. The large variability in visual acuity outcome in the surgical group may be because of complications or progressive cataract. A study of the long-term outcome after macular hole surgery is needed.

The purpose of this article is to describe a clinical finding not previously reported in lens-induced uveitis. An 86-year-old woman was seen by the authors 2 weeks after she had undergone phacoemulsification surgery complicated by retained lens material. A pars plana vitrectomy was indicated. Intraoperatively, retinal arteritis and phlebitis were documented in the retina immediately adjacent to the lens material. This resolved after removal of the material by vitrectomy. This previously unreported finding demonstrates the focal inflammatory effect of the retained lens material on the retinal vasculature.

The purpose of this study was to evaluate the incidence and characteristics of retinal and choroidal manifestations of toxoplasmosis and/or Mycobacterium avium-intracellulare complex (MAC) in patients with acquired immunodeficiency syndrome (AIDS).The authors analyzed their prospectively collected data and found 120 patients with new retinal lesions (group A) that were diagnosed 3 months or longer following the diagnosis of MAC and/or toxoplasmic encephalitis. The authors also performed a point prevalence study of retinal/choroidal findings in 25 consecutive AIDS patients (group B) without known eye disease who had been recently treated for toxoplasmic encephalitis and/or disseminated MAC infections. In addition, the characteristics of retinochoroidal toxoplasmosis scars in 5 AIDS patients were studied and compared with the characteristics of scars in 18 immunocompetent patients.In this study the incidence of ocular manifestations of MAC was zero (95% confidence interval [CI] 0.0% to 3.8%). Two of 25 patients (8%) (95% CI 1% to 26%) in group A and 2 of 11 patients (18.1%) (95% CI 3.3% to 51.8%) in group B had toxoplasmic retinochoroiditis.In AIDS patients, ocular manifestations of toxoplasmosis are more common than ocular MAC. In addition, when compared with immunocompetent patients, AIDS patients tend to have retinochoroidal scars with less retinal pigment epithelium hyperplasia (1.8+ vs 3+) (P = .03).

The purpose of this study is to report retinal manifestations of lues in human immunodeficiency virus (HIV)-positive patients and to suggest a method for treatment of rhegmatogenous retinal detachments in these patients. Two HIV-positive patients with bilateral retinitis were examined and treated at the authors' institution for a period of 14 months. Ocular syphilis was diagnosed clinically, confirmed by cerebrospinal fluid serologic testing, and treated with intravenous penicillin. Both patients experienced bilateral rhegmatogenous retinal detachments complicated by proliferative vitreoretinopathy after resolution of the active retinitis. All four eyes underwent surgical repair with trans pars plana vitrectomy, epiretinal membrane delamination, gas-fluid exchange, endolaser, scleral buckle, and silicone oil instillation. The recognition of ocular syphilis as a cause of retinal detachment in HIV-positive patients is important. Prompt intervention with the appropriate medical and surgical treatments may result in the preservation of vision in these patients.

To determine the risks and benefits of vitrectomy surgery in eyes with stage 2 macular holes.A multicentered, controlled, randomized clinical trial was performed with participation of 16 community and university-based ophthalmology clinics. Thirty-six eyes with stage 2 macular holes and 12 months of follow-up were studied. Pars plana vitrectomy with separation of the posterior hyaloid membrane and intraocular injection of perfluoropropane (C3F8) was followed by postoperative face-down positioning for two weeks. This protocol was compared with observation alone. Outcome variables included anatomic closure of the macular hole, macular hole size, and four standardized measures of vision.At 12 months, 15 (71%) of 21 eyes randomly assigned to observation progressed to stages 3 or 4, compared with three (20%) of 15 eyes randomly assigned to surgery (P.006). Compared with eyes randomly assigned to observation, eyes randomly assigned to surgery had significantly smaller hole diameters (P.01) and significantly better visual acuity outcomes, as measured by the Word Reading (P = .02) and Potential Acuity Meter (P = .002) charts. No significant differences were found for the Early Treatment Diabetic Retinopathy Study chart and Contrast Sensitivity test.Compared with observation alone, surgical intervention in stage 2 macular holes resulted in a significantly lower incidence of hole enlargement and appeared to be associated with better outcome in some measures of visual acuity.

To describe the echographic characteristics of splitting the outer posterior cortical vitreous in patients with proliferative diabetic retinopathy and vitreous hemorrhage.The authors retrospectively reviewed the echographic findings in 270 patients who were evaluated at the Doheny Eye Institute between January 1983 to December 1989 for proliferative diabetic retinopathy and vitreous hemorrhage. None of the eyes had undergone pars plana vitrectomy before echographic examination.Forty-five patients (17%) had echographic evidence of splitting of the outer posterior vitreous cortex, a finding the authors have termed posterior vitreoschisis. In all patients, differentiation of the posterior vitreoschisis from a true posterior hyaloid detachment was possible, either on the initial or on serial echographic examination, by the separate detachment of the inner wall of the vitreoschisis cavity and the true posterior hyaloid from the retinal surface. The vitreoschisis cavities often were found to contain unclotted blood. In some eyes, the inner wall of the vitreoschisis cavity was adherent to the apex of the most highly elevated area of traction retinal detachment, suggesting that posterior vitreoschisis may itself result in clinically significant vitreoretinal traction, independent of the presence or extent of true posterior hyaloid separation.The authors' finding suggest that spontaneous splitting of the outer posterior vitreous cortex may occur in patients with proliferative diabetic retinopathy and vitreous hemorrhage, which may mimic a true posterior cortical vitreous detachment on echographic examination. Preoperative recognition of posterior vitreoschisis may be important in the surgical management of these patients.

The authors determine the intraocular tolerance of a new widely used liquid perfluorocarbon, perfluoroctylbromide (perflubron).Pars plana vitrectomy was performed on 54 eyes of 54 patients with vitreoretinal disorders at three centers. Diagnoses included giant retinal tears, proliferative vitreoretinopathy, and dislocated intraocular and crystalline lenses. At the conclusion of the vitrectomy, perflubron was removed.Perflubron was efficacious for vitreoretinal manipulation. Of the 45 eyes with retinal detachment, 23 (51.1%) of the retinas were reattached after a single surgery; redetachment occurred in 22 (48.9%) after the initial procedure, and further surgery was necessary to reattach the retina. Final retinal reattachment was achieved in 40 (88.9%) eyes. Mean visual acuity improvement was six lines (P0.0019). Visualization of the water/perfluorocarbon interface was good. There was no evidence of adverse effects from perflubron on the retina, lens, or anterior segment.Findings indicate that perflubron is safe for temporary intraoperative use intravitreally. The absence of adverse effects is consistent with the properties of perflubron that our group has studied in the eyes of animals and in other uses in human patients.

The purpose of this study is (1) to determine baseline characteristics and natural history of immature full-thickness macular holes, (2) to describe progression and resolution, and (3) to present new aspects of pathogenesis of idiopathic macular hole.The authors analyzed 41 eyes with stage 2 macular holes (37 patients) in a multicentered prospective randomized trial; 19 eyes were randomized to observation (versus surgery) and had more than 12 months of follow-up, allowing determination of the natural course. Baseline and subsequent examinations included best-refracted visual acuity (Early Treatment of Diabetic Retinopathy Study, potential acuity meter, Pelli-Robson contrast sensitivity, and Bailey-Lovie reading vision), of clinical examinations, photography, and fluorescein angiography.Mean Snellen visual acuity was 20/66 at baseline. Centric holes usually had a small break (201 microns average mean diameter) with a dark yellow ring and without significant retinal elevation. Eccentric holes had a high maximum/minimum diameter ratio (mean, 1.88 +/- 0.7) and an incomplete cuff of subretinal fluid or yellow ring. Posterior vitreous detachment prevalence was 32% (8/25) in the centric hole group and 0% (0/ 16) in the eccentric hole group (P0.05). For the 19 eyes with 12 months of followup, progression rate to stage 3 (or 4) was 74% (n = 14). The diameter of the stage 2 holes increased significantly between baseline and 12 months (P0.001). Progression rate to stage 3 was 100% (8/8) in the eyes with pericentral hyperfluorescence (PCH) and 55% (6/11) in eyes without PCH (P0.05). Enlargement occurred in 100% of eccentric holes and 60% of centric holes (P = 0.09). Different progression patterns in eccentric and centric holes suggest different mechanisms of pathogenesis.Eccentric and centric stage 2 macular holes may have a different pathogenesis. Most stage 2 macular holes, especially with PCH (P0.05) or eccentric holes, progressed to stage 3 or 4. In addition to purely tangential traction, some component of obliquely oriented anteroposterior vitreous traction component may be important for pathogenesis of senile macular holes, particularly eccentric stage 2 macular holes.

HLA phenotype and immune responses to CMV were studied to determine whether the subset of AIDS patients who developed CMV retinitis were immunogenetically or immunologically predisposed. CMV retinitis develops in approximately 28-35% of AIDS patients and CMV encephalitis develops in 40% of those with retinitis, often leading to death. T-cell proliferation responses to CMV and HIV were assayed prospectively in individuals enrolled in a longitudinal study at the HIV Neurobehavioral Research Center (HNRC) in San Diego. Seventy-three participants, at various stages of disease, have been HLA typed and followed, clinically and immunologically, for up to 5 years. Six HIV infected individuals who eventually developed CMV retinitis, and were assayed prospectively, had a history of low T-cell proliferation to CMV antigens before they were profoundly immunosuppressed. All 10 individuals with CMV retinitis had at least one of three HLA alleles (or combinations): A2B44 (p = 0.02), B51(p = 0.02), or DR7 (p = 0.01) (collective p value = 0.007). Three of the 10 had two or more of these alleles. Of AIDS patients with CD4 counts below 100 and actively at risk for retinitis, 7/15 with A2B44,51, or DR7 have developed retinitis compared to 0/13 without these HLA alleles (relative risk = 23.8). All 4 patients with these alleles who have died, had retinitis. These results suggest that HIV infected individuals with HLA phenotypes A2B44, B51, and DR7 have low T-cell immune responses to CMV and are predisposed to CMV retinitis and encephalitis as immunodeficiency progresses.

We present new Spitzer/IRS spectra of two hot R Coronae Borealis (RCB) stars, one in the Galaxy,V348 Sgr, and one lying in the LMC, HV 2671. These two objects may constitute a link between the RCB stars and the late Wolf-Rayet ([WCL]) class of central stars of planetary nebula (CSPNe) such as CPD -56 8032 that has little or no hydrogen in their atmospheres. HV 2671 and V348 Sgr are members of a rare subclass that has significantly higher effective temperatures than most RCB stars, but sharing the traits of hydrogen deficiency and dust formation that define the cooler RCB stars. The [WC] CSPNe star, CPD -56 8032, displays evidence for dual-dust chemistry showing both PAHs and crystalline silicates in its mid-IR spectrum. HV 2671 shows strong PAH emission but shows no sign of having crystalline silicates. The spectrum of V348 Sgr is very different from those of CPD -56 8032 and HV 2671. The PAH emission seen strongly in the other two stars is not present. Instead, the spectrum is dominated by a broad emission centered at about 8.2 micron. The mid-IR spectrum of CPD -56 8032 shows emission features that may be associated with C60. The other two stars do not show evidence for C60. HV 2671 has also been detected by Herschel/PACS and SPIRE. V348 Sgr and CPD -56 8032 have been detected by AKARI/FIS. These data were combined with Spitzer, IRAS, 2MASS and other photometry to produce their spectral energy distributions from the visible to the far-IR. Monte Carlo radiative transfer modeling was used to study the circumstellar dust around these stars. HV 2671 and CPD -56 8032 require both a flared inner disk with warm dust and an extended diffuse envelope with cold dust to to fit their SEDs. The SED of V348 Sgr can be fit with a much smaller disk and envelope., Comment: 20 pages, 5 figures, accepted for publication in The Astronomical Journal

This prospective, randomized, multicenter, controlled trial was designed to evaluate the efficacy and safety of intravenous ganciclovir for the treatment of peripheral cytomegalovirus (CMV) retinitis in patients with AIDS. Patients were randomly assigned to receive either immediate treatment, intravenous ganciclovir, 5 mg/kg twice daily for 14 days followed by 5 mg/kg once daily for 14 weeks, or deferred treatment. Patients randomized to deferred treatment whose retinitis progressed were offered ganciclovir. Of the 22 patients randomized to deferred treatment who were included in the final analysis, 20 were found to have progressive CMV retinitis compared with 10 of the 13 randomized to immediate treatment. The median time to progression in the deferred treatment group, as determined by a masked fundus photography reading center, was 13.5 days compared with 49.5 days in the immediate treatment group (mean +/- SD, 19.3 +/- 4.1 vs. 66.4 +/- 14.0; P = .001, log rank test). These data indicate that ganciclovir delays the progression of CMV peripheral retinitis in persons with AIDS.

Ophthalmic lasers are used as diagnostic as well as therapeutic modalities in patients with retinal diseases. Recent advances in laser technology have allowed more convenient selection of wavelength and a wide variety of delivery systems is available to deliver the laser energy to the retina. In addition, newer lasers that disrupt and cut tissue will become available for use in patients with retinal diseases. The use of imaging lasers and lasers in combination with dyes selectively to enhance their effects have become useful in diagnosis and understanding of pathophysiology of diseases. These lasers will also be therapeutically useful. This manuscript delineates the new types of diagnostic and therapeutic lasers, new imaging dyes and techniques as they apply to retinal diseases as well as the principles of laser-tissue interaction as applied to the retina. This should allow the ophthalmologist who treats patients with retinal diseases to make more intelligent decisions regarding the use and acquisition of laser systems.

Cotton-wool spots and cytomegalovirus (CMV) retinitis are seen frequently in AIDS patients. Human immunodeficiency virus (HIV) infection of the retina has been proposed as a mechanism for the high incidence of retinal pathology. An autopsy study of the eyes from 25 consecutive cases of AIDS was performed using gross examination, light microscopy, trypsin digestion of retinal vasculatures, and immunohistochemistry to evaluate the possible role of HIV, as well as CMV, in the pathogenesis of retinitis and retinal vasculopathy. Brain tissue was studied in the first 20 of these cases to evaluate any correlation between retinal and central nervous system pathology. CMV retinitis was observed in 15 cases (60%). Cotton-wool spots were seen in nine cases (36%). CMV encephalitis was detected in four cases, whereas HIV encephalitis was noted in five cases. We were unable to demonstrate a correlation between CMV retinitis and CMV encephalitis. However, the number of cases studied was small, and the frequency of CMV encephalitis was low. On the other hand, bilateral CMV retinitis demonstrated a correlation to HIV encephalitis (P less than 0.005, Fisher's exact test). HIV infection of the retina was not detected by typical morphologic changes or immunohistochemistry. Immunohistochemistry localized CMV infection solely to areas of active retinitis. These findings suggest that bilateral CMV may serve as a marker of HIV encephalitis, possibly indicating a severely immunodepressed state.(ABSTRACT TRUNCATED AT 250 WORDS)

Infectious retinitis and proliferative vitreo-retinopathy (PVR) are two disorders in which there is a need for antiviral and antiproliferative drugs to be delivered to the retina giving therapeutic levels over intervals of weeks to months. Currently, intravitreal ganciclovir is given to AIDS patients with cytomegalvirus rentinitis who are intolerant or unwilling to take ganciclovir intravenously. Antimetabolites capable of inhibiting PVR would be an important therapeutic modality; treatment trails with intraocular irrigation of daunorubicin are currently underway. We have explored the intraocular toxicity of polar anti-CMV drugs and anti-proliferative agents which we have previously shown can be incorporated into a multivesicular liposome system. We have shown that these drugs are not toxic at concentrations many times above those necessary for therapeutic effect when injected intravitreally. We will review electrophysiologic and morphologic data on the toxicity of both the drugs and their liposome preparations injected intravitreally. Our laboratory studies suggest that certain polar antiviral and antimetabolite drugs can be delivered at efficacious concentrations without evidence of toxicity in animal models.

We present three cases of large intraoperative or postoperative hemorrhagic choroidal detachment with subsequent adherence of the retina to anterior segment structures. Surgical management involved bimanual vitrectomy through anterior sclerotomy sites and dissection within the anterior segment. Successful retinal reattachment was achieved in two of these cases (18-months' follow up). In the third case, the retina remained attached for 4 months but then redetached.

Straight, 30-, and 45-degree endolaser probes were compared to determine the optimal curve for peripheral endolaser photocoagulation during pars plana vitrectomy. The 30-degree probes allowed panretinal laser coverage in phakic eyes, thereby negating the need for peripheral cryopexy which may cause increased inflammation and contribute to the development of proliferative vitreoretinopathy. The 30-degree probe was less likely to strike the lens inadvertently, produced a more consistent burn, was more versatile in posterior treatments, and had a longer fiberoptic core life than the 45-degree probe. It was impossible to treat the peripheral retina using the straight probe without hitting the lens during phakic pars plana vitrectomy.

The authors report four cases in which retinal biopsy findings yielded unexpected or previously unreported diagnoses in patients with inflammatory retinitis. The tissue diagnoses included Wegener's retinal vasculitis in an immunosuppressed patient with a clinical diagnosis of cytomegalovirus retinitis, a novel viral form in the retina of a patient with cytomegalovirus retinitis, a case of acute retinal necrosis due to cytomegalovirus infection in an immunologically normal adult, and a case of ganciclovir-resistant herpes family viral retinitis. These cases illustrate the use of retinal biopsy in obtaining tissue for diagnosis and guiding treatment in selected cases of retinitis.