Rajiv Anand

Laser treatment in fellow eyes with large drusen: Updated findings from a pilot randomized clinical trial

PURPOSE To update the findings from the Choroidal Neovascularization Prevention Trial (CNVPT) with respect to resolution of drusen, incidence of choroidal neovascularization, and visual function. DESIGN A multicenter, randomized, controlled, pilot clinical trial. PARTICIPANTS The 120 patients enrolled in the CNVPT. Patients had signs of choroidal neovascularization or retinal pigment epithelial detachment in 1 eye and had >/=10 large (>63- micro m) drusen in the contralateral, or fellow, eye. INTERVENTION The fellow eye of 59 patients was assigned randomly to argon green laser treatment consisting of multiple 100- micro m spots at least 750 micro m from the center of the fovea. The fellow eye of the remaining 61 patients was assigned randomly to observation. MAIN OUTCOME MEASURES Change in visual acuity was the primary outcome measure. Incidence of choroidal neovascularization, resolution of drusen, change in contrast threshold, change in critical print size for reading, and incidence of geographic atrophy were secondary outcome measures. RESULTS Throughout 4 years of follow-up, there were no statistically significant differences in change in visual acuity, contrast threshold, critical print size, or incidence of geographic atrophy. With additional follow-up, the large increase in the incidence of choroidal neovascularization observed within 18 months of treatment was maintained; however, by 30 months, the incidence in the two treatment groups was the same. Most drusen resolution in treated eyes occurred within 24 months of the initial treatment. Treated eyes that received higher-intensity laser burns had an increased risk of choroidal neovascularization. Among eyes developing choroidal neovascularization in each treatment group, most lesions (two thirds or more) were composed of occult neovascularization only. CONCLUSIONS Laser treatment as applied in the CNVPT caused an excess risk of choroidal neovascularization in the first year or so after treatment. The increased early incidence of choroidal neovascularization was not associated with either a harmful or beneficial effect in this pilot study.

Influence of the cannulated vitrectomy system on the occurrence of iatrogenic sclerotomy retinal tears.

Purpose: To determine whether the use of the cannulated vitrectomy system decreases the incidence of sclerotomy‐related retinal tears relative to traditional vitrectomy techniques. Methods: Forty‐one eyes of 77 patients in this study were randomly selected to undergo treatment with the cannulated port system. Results: We demonstrated a statistically significant decreased incidence of sclerotomy tears in the cannulated group relative to the noncannulated group (1% vs. 7.7%, P < 0.05). The benefit of the cannulated port system appears to be greatest in cases in which an inexperienced surgeon is learning the techniques of vitreoretinal surgery, in eyes with a preoperative diagnosis of tractional diabetic detachment, and in surgery requiring membrane delamination (simple and extensive). Conclusion: The three‐port vitrectomy system decreases the incidence of sclerotomyrelated retinal tears. RETINA 17:430‐433, 1997

Characterization of sterile intraocular inflammatory responses after intravitreal bevacizumab injection.

Purpose: The purpose of this study was to determine the frequency and characteristics of sterile intraocular inflammation occurring after intravitreal bevacizumab (IVB) (Avastin, Genentech, South San Francisco, CA) injection and to analyze whether a repeat IVB or intravitreal ranibizumab (IVR) (Lucentis, Genentech) injection after an episode of postinjection inflammation elicits a repeat inflammatory reaction. Methods: A retrospective case series evaluated 16,166 IVB injections administered between 2006 and 2008. Patients with postinjection inflammation were analyzed for the number of previous injections, time from prior injection to incident injection, presenting signs and symptoms, treatment, visual acuity, time from onset to resolution and recovery of vision, and whether repeat injection caused recurrent inflammation. Results: The incidence of sterile intraocular inflammation after IVB injection resolving with topical antibiotics and steroids alone was 0.27% (44 of 16,166). The average number of prior IVB injections in the ipsilateral eye was 2.8 ± 0.4 with 10 cases occurring with first-time injections. The average time from injection to recovery of visual acuity was 53 ± 18 days, and from injection to resolution of inflammation was 37 ± 5 days. Thirty-six cases received subsequent IVB or intravitreal ranibizumab, and there were three episodes of recurrent inflammation with repeat IVB. The average follow-up was 17 ± 1 month. Conclusion: In most cases of sterile intraocular inflammation after IVB, visual acuity returned to baseline, and intraocular inflammation rarely recurred with repeat IVB or intravitreal ranibizumab.

Orbital Infarction Syndrome after Surgery for Intracranial Aneurysms

Background: Global orbital infarction results from ischemia of the intraocular and intraorbital structures due to hypoperfusion of the ophthalmic artery and its branches. Patients: The authors describe six patients in whom acute proptosis, ophthalmoplegia, and blindness developed immediately after surgery for intracranial aneurysms. Results: All patients underwent standard frontotemporal craniotomies to clip their aneurysms. In all patients, proptosis, ophthalmoplegia, and blindness developed in the immediate postoperative period; fundus abnormalities included retinal edema, retinal arteriolar narrowing and other vascular abnormalities, and pale optic disc swelling. Some patients had facial and corneal anesthesia. Ophthalmoplegia and facial anesthesia improved in most patients, but none regained any vision in the affected eye. Conclusion: Orbital infarction syndrome is a rare complication of neurosurgical procedures. Increased orbital pressure probably reduced ophthalmic artery and collateral arterial perfusion, resulting in ischemia of the intraocular and intraorbital structures. There may be multiple factors that compound the risk for orbital infarction, and patients with subarachnoid hemorrhage, increased intracranial pressure, anomalous arterial or venous circulation, or impaired orbital venous outflow seem particularly vulnerable.

Macular Pseudoholes Clinical Features and Accuracy of Diagnosis

BACKGROUND Epimacular membrane with pseudohole is an important vitreomacular disorder that belongs in the differential diagnosis of impending and established macular hole. To better characterize this lesion, the authors attempted to identify various features of eyes with epimacular membrane and pseudohole. METHODS Demographic, clinical, photographic, and fluorescein angiographic data for 14 eyes with epimacular membrane and pseudohole were reviewed. Horizontal and vertical diameters of the pseudoholes were measured, and the original diagnosis was recorded for each eye. Fluorescein angiography was performed in 11 eyes. RESULTS The mean age of patients with macular pseudoholes was 61.6 years, and median visual acuity for pseudohole eyes was 20/30. Mean horizontal and vertical diameters of the pseudoholes were 384 and 410 microns, respectively. None of the eyes with pseudoholes had the characteristic ophthalmoscopic features associated with full-thickness macular holes or impending macular holes. Results of fluorescein angiography showed three eyes with increased tortuosity or abnormal straightening of the perifoveal vessels; three eyes with a foveal window defect; and three eyes with late leakage from the perifoveal vessels. The original diagnosis of the initial examining physician was correct in only 43% of eyes with epimacular membrane and pseudohole. CONCLUSION Epimacular membrane with pseudohole may be an underdiagnosed lesion and commonly mistaken for impending macular hole, full-thickness hole, or lamellar hole. These data may be of use as more patients are being considered for recently advocated surgical treatments for impending and established macular hole.

Rejection of intraocular tumors from transgenic mice by tumor-infiltrating lymphocytes

The present study examined the role of tumor infiltrating lymphocytes (TIL) in the rejection of intraocular tumors from SV40 transgenic mice. Tumor cells from an intraocular tumor arising in an SV40 transgenic FVB/N mouse were transplanted into the eyes of syngeneic FVB/N mice and the TIL isolated. TIL were assessed for direct cytolytic activity in vitro. TIL were also transferred passively to immunosuppressed FVB/N mice to determine if they could mediate intraocular tumor rejection. The role of CD4+ and CD8+ T cells in intraocular tumor rejection was evaluated by depleting the respective cell populations in FVB/N hosts prior to intraocular tumor challenge. The results showed that intraocular tumors undergoing rejection in immunocompetent syngeneic hosts became infiltrated with T cells, with the CD8+ subset predominating at the time of rejection. By contrast, athymic nude mice did not reject the intraocular tumors nor did the tumors become infiltrated with TIL. TIL displayed direct, tumor-specific cytolytic activity immediately after isolation from the tumor-containing eyes. FVB/N hosts depleted of CD4+ T cells were unable to reject their intraocular tumors. In vivo depletion of CD8+ T cells delayed, but did not prevent tumor rejection. Adoptively transferred TIL mediated swift rejection of intraocular tumors in immunoincompetent recipients. Recipients of TIL, but not recipients of normal spleen cells, acquired significant tumor-specific CTL activity that was demonstrable in vitro. The results strongly suggest, but do not prove, that TIL mediate rejection of intraocular tumors from transgenic mice by direct cytolysis. Although CD4+ T cells are necessary for tumor rejection and are capable of direct cytolysis, the predominant effector cells are CD8+ CTL.

Effect of anti-ganglioside antibodies on the metastatic spread of intraocular melanomas in a nude mouse model of human uveal melanoma

In vivo and in vitro studies were performed to determine: (a) if human uveal melanoma cells expressed GD2 and GD3 gangliosides; (b) if anti-GD2 monoclonal antibodies would inhibit the propensity of human uveal melanoma cells to localize in the liver following intravenous injection; and (c) if anti-GD2 monoclonal antibody would reduce the spontaneous metastasis of primary intraocular melanomas in nude mice. The results showed that all three of the human uveal melanoma cell lines tested expressed GD2 and GD3 gangliosides in vitro and in vivo. The human uveal melanoma cell lines preferentially localized in the liver and entered the hepatic parenchyma following spontaneous metastasis from the eyes of nude mice. In vivo administration of anti-GD2 monoclonal antibody produced a sharp reduction in the number of uveal melanoma cells that disseminated to the liver following either intravenous injection or by spontaneous metastasis from primary intraocular melanomas. Collectively, the results demonstrate that uveal melanoma cells display a propensity to localize in the liver after entering the bloodstream; however, this localization can be significantly inhibited by in vivo administration of anti-ganglioside antibodies. The expression of GD2 and GD3 surface gangliosides on uveal melanomas and the capacity of anti-ganglioside antibodies to inhibit metastasis formation in mouse models of ocular and cutaneous melanomas raise the possibility of implementing anti-ganglioside antibodies as potential therapeutic agents for the management of uveal melanoma.

Initial experience with an eight-month sustained-release intravitreal ganciclovir implant for the treatment of CMV retinitis associated with AIDS.

BACKGROUND AND OBJECTIVE An intravitreal device administering ganciclovir in a sustained-release fashion has been developed for site-specific therapy of cytomegalovirus (CMV) retinitis. The initially tested devices released ganciclovir at a rate of approximately 2 micrograms/hour (Mark I device), yielding an estimated in vivo therapeutic life span of 4 months. This report describes the initial clinical results of a longer-lasting device that releases ganciclovir at a rate of 1 microgram/hour (Mark II device), designed to be effective for up to 8 months. PATIENTS AND METHODS Over a 15-month time period, a total of 39 Mark II intravitreal ganciclovir devices were placed in 35 eyes of 29 patients with a diagnosis of CMV retinitis. At the time of implantation, none of the patients were on systemic anti-CMV therapy. RESULTS Of the first 29 eyes of the 29 enrolled patients implanted with their initial Mark II device, 28 (97%) had no progression of retinitis at the 4-week postoperative examination. Survival analysis of these initial 29 implants revealed the median time to disease progression was 29.3 weeks (205 days). Serious ocular complications included one case of acute bacterial endophthalmitis (2.9% of eyes or 2.5% of implantations), and four cases of rhegmatogenous retinal detachment (four of 35 or 11.4% of eyes). Of the 10 patients with initially unilateral retinitis, four (40%) eventually developed contralateral disease. Five clinically suspected cases of extraocular, systemic CMV disease occurred during the study (17.2% of patients), necessitating reinstitution of systemic therapy. CONCLUSION This small, uncontrolled pilot study indicates that the Mark II (1 mg/hour) sustained-release intravitreal ganciclovir device is effective for local control of CMV retinitis.

Capacity of simian virus 40 T antigen to induce self-tolerance but not immunological privilege in the anterior chamber of the eye.

Transgenic mice bearing the simian virus 40 (SV40) large T oncogene developed progressively growing intraocular tumors and displayed characteristics of immunological tolerance to SV40 T antigen. Transgenic mice failed to mount CTL responses to SV40 T antigen-bearing tumor cell lines derived from the transgenic intraocular tumors. Spleen cells from transgenic hosts were able to prevent the in vivo and in vitro generation of CTL responses by lymphocytes from normal syngeneic FVB/N mice. Adoptive transfer of spleen cells from tolerant transgenic donors temporarily inhibited the immunological rejection of SV40 T antigen-positive tumor cells transplanted to normal syngeneic FVB/N recipients. Thus, introduction of SV40 transforming sequences into the mouse germline induced tolerance to SV40 T antigen. However, in normal FVB/N mice, SV40 T antigen-bearing tumor cells failed to experience immune privilege in the anterior chamber and did not elicit systemic down-regulation of delayed-type hypersensitivity responses that characteristically occur when antigens are introduced into the anterior chamber. The results indicate that within the anterior chamber of the eye, SV40 T antigen-bearing cells are perceived by the hosts immune system much differently than are other categories of antigen. Thus, SV40 T antigen effectively induces self-immunological tolerance when its gene is introduced into the hosts germline but fails to experience immunological privilege in the anterior chamber of the eye in normal hosts.

Pseudohypopyon in unilateral acute idiopathic maculopathy

Abstract: Unilateral acute idiopathic maculopathy (UAIM) is a recently described condition in young adults consisting of rapidly progressive central visual loss, gray-white opacification of the outer retina, and serous detachment of the macula. Bulls eye pattern pigmentary changes may occur in the macula after resolution of the acute phase of the disease. A case of UAIM in which a shifting of subretinal inflammatory infiltrate was observed is reported. This is the tenth reported case of UAIM, and represents a variation in the clinical presentation of this disease. The appearance and the shifting of the subretinal infiltrate seen in this patient support an inflammatory etiology of UAIM.