Deepak P. Edward

A PATHOLOGIC STUDY OF PHOTORECEPTOR CELL DEATH IN RETINAL PHOTIC INJURY

In the studies of retinal photic injury in the rat model, about 14-47% of the photoreceptor cell loss occurs in the first 24 hours. To understand the mechanism of this massive cell death and subsequent dissolution, we studied the early morphologic changes and examined the effect of cycloheximide, a protein synthesis inhibitor, on photic injury in rats. Groups of 2 dark-adapted albino Lewis rats were sacrificed immediately after 8, 16 or 24 hr of continuous exposure to green fluorescent light (intensity, 160-180 foot-candles; wavelength, 490-560 nm). An additional 2 rats were sacrificed 8 hr after a 24 hr light exposure, and 2 animals served as unexposed controls. The morphologic findings of the degenerating photoreceptor cells were assessed by light and electron microscopy. The integrity of the nuclear chromatin was investigated using a monoclonal anti-DNA antibody. Most of the photoreceptor cell loss was observed between 16 and 24 hr of exposure. No inflammatory or macrophagic cells were seen. Different stages of nuclear condensation and chromatin margination could be defined. The chromatin showed a progressive decrease in DNA labelling density. Scattered photoreceptor cells showed early cytoplasmic densification. To study the effect of cycloheximide, 4 rats were treated with 5 mg/kg subcutaneously at the start of a 24 hr exposure period and were sacrificed 6 hr after the exposure. Four untreated animals served as exposed controls for morphometric comparison of the outer nuclear layer (ONL). The control rats showed a 24% decrease in the thickness of the ONL when compared to cycloheximide-treated rats (p less than 0.001). The observations of mitochondrial changes and early DNA digestion were consistent with necrosis as the mechanism of cell death. However, in scattered photoreceptor cells, cytoplasmic densification, margination of nuclear chromatin, the lack of associated inflammation and the protective effect of cycloheximide were suggestive of apoptosis as another mechanism of cell death.

Endophthalmitis associated with the Ahmed glaucoma valve implant

Aim: To investigate the rate, risk factors, clinical course, and treatment outcomes of endophthalmitis following glaucoma drainage implant (GDI) surgery. Methods: A computerised relational database search was conducted to identify all patients who were implanted with Ahmed glaucoma valve (AGV) and developed endophthalmitis following surgery at the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia, between 1 January 1994 and 30 November 2003. Only medical records of the patients who developed endophthalmitis were retrospectively reviewed. Results: 542 eyes of 505 patients who were on active follow up were included in the study. Endophthalmitis developed in nine (1.7%) eyes; the rate was five times higher in children than in adults. Delayed endophthalmitis (developed 6 weeks after surgery) occurred in eight of nine eyes. Conjunctival erosion overlying the AGV tube was present in six of nine eyes. Common organisms isolated in the vitreous included Haemophilus influenzae and Streptococcus species. Multiple regression analysis revealed that younger age and conjunctival erosion over the tube were significant risk factors associated with endophthalmitis. Conclusion: Endophthalmitis is a rare complication of GDI surgery that appears to be more common in children. Conjunctival dehiscence over the GDI tube seems to represent a major risk factor for endophthalmitis. Prompt surgical revision of an exposed GDI tube is highly recommended.

Visual Acuity and Intraocular Pressure after Descemet's Stripping Endothelial Keratoplasty in Eyes with and without Preexisting Glaucoma

PURPOSE (1) To characterize the pattern of intraocular pressure (IOP) changes after Descemets stripping endothelial keratoplasty (DSEK) in patients without preexisting glaucoma and in those with preexisting glaucoma, with and without prior glaucoma surgery. (2) To compare vision and IOP outcomes among the 3 groups. DESIGN A retrospective chart review. PARTICIPANTS A total of 805 DSEK cases performed in 641 patients by a single surgeon from December 2003 to August 2007 were available in the database. Only the first-treated eye of each patient with at least 1-year follow-up was included. Four hundred cases qualified: 315 eyes had no glaucoma (C); 64 eyes had glaucoma with no previous glaucoma surgery (G); and 21 eyes had prior glaucoma surgery (GS). Eyes with preexisting retinal problems were included in the analysis. METHODS Data analysis included calculation of incidence of postoperative IOP elevation. The study criteria for postoperative IOP elevation were IOP > or =24 mmHg or IOP increase > or =10 mmHg from baseline. Kruskal-Wallis test was used to compare visual acuity (VA) and IOP among the 3 groups preoperatively and at 1-, 3-, 6-, and 12-month postoperative visits. MAIN OUTCOME MEASURES Visual acuity (Snellen) and IOP (millimeters of mercury). RESULTS The incidence of postoperative IOP elevation by the study criteria was 35%, 45%, and 43% for groups C, G, and GS, respectively. Elevated IOP was medically managed by initiating or increasing glaucoma medications or reducing steroids in 27%, 44%, and 38% of the patients in groups C, G, and GS, respectively. A subsequent glaucoma procedure was performed in 0.3%, 5%, and 19% of patients in groups C, G, and GS, respectively. Only the control group had statistically significant IOP elevation at 12 months (median increase of 2 mmHg) when compared with baseline (P<0.0001). All 3 groups had statistically significant improvement in vision at 12 months when compared with baseline (12-month median VA = 20/40 for C and G; and 20/50 for GS, P<0.0001). CONCLUSIONS All groups had a substantial incidence of IOP elevation after DSEK. Close monitoring of IOP is warranted. In this cohort, preexisting glaucoma did not seem to have a negative effect on VA after DSEK. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Corneal pathology in microphthalmia with linear skin defects syndrome.

PURPOSE To describe the histopathology of the cornea in microphthalmia with linear streaks (MLS) syndrome. METHODS Two patients with MLS syndrome underwent penetrating keratoplasty. This study describes the histopathology and investigates immunophenotype of the corneal extracellular matrix by using keratan sulfate and collagen type III antibodies. RESULTS Clinical examination revealed bilateral sclerocornea and characteristic skin changes. By light microscopy, central corneal stroma in both patients showed vascularization and irregular thick collagen lamellae typical of sclerocornea. In addition, corneal thinning, anterior synechiae, and the absence of the Descemet membrane were noted, which was suggestive of Peters anomaly. Diffuse and intense anti-keratan sulfate staining and minimal anti-collagen type III stromal staining were seen in both corneal buttons. CONCLUSIONS The cornea in MLS may clinically resemble sclerocornea. Histologic features resemble those previously described in sclerocornea and also seen in anterior segment dysgeneses. Keratan sulfate and collagen type III labeling suggests that the corneal extracellular matrix resembled cornea and not sclera.Objective:To examine characteristics of circumcised and uncircumcised Latino and black men who have sex with men (MSM) in the United States and assess the association between circumcision and HIV infection. Methods:Using respondent-driven sampling, 1154 black MSM and 1091 Latino MSM were recruited from New York City, Philadelphia, and Los Angeles. A 45-minute computer-assisted interview and a rapid oral fluid HIV antibody test (OraSure Technologies, Bethlehem, PA) were administered to participants. Results:Circumcision prevalence was higher among black MSM than among Latino MSM (74% vs. 33%; P < 0.0001). Circumcised MSM in both racial/ethnic groups were more likely than uncircumcised MSM to be born in the United States or to have a US-born parent. Circumcision status was not associated with prevalent HIV infection among Latino MSM, black MSM, black bisexual men, or black or Latino men who reported being HIV-negative based on their last HIV test. Further, circumcision was not associated with a reduced likelihood of HIV infection among men who had engaged in unprotected insertive and not unprotected receptive anal sex. Conclusions:In these cross-sectional data, there was no evidence that being circumcised was protective against HIV infection among black MSM or Latino MSM.

Driving performance of glaucoma patients correlates with peripheral visual field loss.

Purpose:To identify clinical vision measures that are associated with the driving performance of glaucoma patients who have visual field loss and visual acuity better than 20/100 and to compare the driving performance of glaucoma patients with the driving performance of a group of age- and sex-equivalent individuals without eye disease. Patients:Forty patients with glaucoma and 17 normally sighted control subjects participated in this study. Methods:Clinical vision data, consisting of visual acuity, letter contrast sensitivity, and visual fields, were collected. Driving performance was assessed by (1) an interactive driving simulator that measured 7 indices of performance (including number of accidents) and (2) the self-reported accident involvement for the past 5 years. Main Outcome Measures:Driving simulator performance and real-world, self-reported accident involvement. Results:The number of accidents as measured on the driving simulator in the glaucoma group was significantly correlated with three Goldmann visual field measures: combined horizontal extent (ρ = −0.47, P = 0.01), total horizontal extent (ρ = −0.49, P = 0.007), and total peripheral extent (ρ = −0.55, P = 0.002). There were no statistically significant correlations between the driving performance of the glaucoma group and the visual acuity or contrast sensitivity measures. When compared with the control group, a significantly greater proportion of the glaucoma group reported having at least one real-world accident within the past 5 years (Fisher exact test, P = 0.005). Conclusions:Visual field reduced to less than 100° of horizontal extent may place patients with peripheral field loss at greater accident risk. A higher incidence of real-world and simulator accidents was found for the group with glaucoma.

Antiretinal Antibodies in Serum of Patients with Age-related Macular Degeneration

Antibodies, immunoreactive with normal human retinal proteins, were detected by Western immunoblot analysis in the sera of 30 patients with age-related macular degeneration (AMD). Sera from 14 of these patients demonstrated positive binding predominantly to a doublet protein of molecular weight between 58 and 62 kD. The sera from the remaining 16 patients and from 12 control subjects reacted either weakly or not at all with the doublet protein. No correlation was found with any specific type of AMD. The serum antibodies also immunocrossreacted with the same proteins from isolated photoreceptor outer segments; this was confirmed by indirect immunofluorescence on intact retinas. The crossreactivity of the serum antibodies with a protein of Mr 58 to 62 kD, the lower band present in the bovine purified neurofilament-68 kD preparation, suggests strongly that this protein may be a component of the neuronal cytoskeleton. However, it is not clear whether these autoantibodies play a direct role in the etiology of AMD or represent a nonspecific response to retinal damage.

Animal Models of Glaucoma

Glaucoma is a heterogeneous group of disorders that progressively lead to blindness due to loss of retinal ganglion cells and damage to the optic nerve. It is a leading cause of blindness and visual impairment worldwide. Although research in the field of glaucoma is substantial, the pathophysiologic mechanisms causing the disease are not completely understood. A wide variety of animal models have been used to study glaucoma. These include monkeys, dogs, cats, rodents, and several other species. Although these models have provided valuable information about the disease, there is still no ideal model for studying glaucoma due to its complexity. In this paper we present a summary of most of the animal models that have been developed and used for the study of the different types of glaucoma, the strengths and limitations associated with each species use, and some potential criteria to develop a suitable model.

Lacrimal gland tumors and simulating lesions. Clinicopathologic and MR imaging features.

The lacrimal gland region can be involved in a wide spectrum of orbital pathology, including inflammatory, lymphoproliferative, and epithelial tumors. This article focuses on benign and malignant epithelial tumors of lacrimal gland and simulating lesions. The clinical presentations, MR imaging, and pathologic findings of lacrimal gland tumors are reviewed.

Intraocular Pressure Measurements Following Descemet Stripping Endothelial Keratoplasty

PURPOSE The effect of increased corneal thickness after Descemet stripping endothelial keratoplasty (DSEK) on intraocular pressure (IOP) measurement has not been previously studied. It is uncertain if this increase in corneal thickness would artificially elevate IOP reading by Goldmann tonometry [GAT] (Haag-Streit, Konig, Switzerland). Therefore the effect of DSEK-related thick cornea on IOP measurement was investigated using three different techniques. DESIGN Prospective cross-sectional study. METHODS Participants were recruited from a single tertiary referral center. Fifty eyes of 38 patients with successful DSEK at least three months prior to testing were evaluated. At the time of the study, none of the participants had clinically detectable corneal edema. IOP was measured with GAT, pneumatonometry, and dynamic contour tonometry (DCT) in an unmasked randomized sequence. Central corneal thickness (CCT) was measured by ultrasonic pachymetry. RESULTS Mean CCT was 701 +/- 68 microm. The mean IOP +/- standard deviation (SD) was 15.9 +/- 4.9 mm Hg for GAT, 20.3 +/- 4.5 mm Hg for pneumatonometry, and 19.8 +/- 4.4 mm Hg for DCT. Pneumatonometry and DCT IOP measurements were significant higher than GAT (P < .01). In contrast, the difference between pneumatonometry and DCT readings was not statistically significant (P = .28). The correlations between IOP and corneal thickness were not significant in this cohort (P > .05). CONCLUSIONS Falsely elevated GAT, as expected in thick corneas, was not demonstrated after DSEK. High IOP reading by GAT therefore should raise suspicion of elevated IOP in DSEK eyes.

Ocular amyloidosis and secondary glaucoma

OBJECTIVE To report the clinical and histopathologic findings in two cases of secondary glaucoma associated with amyloidosis. DESIGN Two case reports. METHODS Retrospective review of clinical findings, course, and treatment of the two patients. The histopathologic findings from available biopsy material were also reviewed. MAIN OUTCOME MEASURES Intraocular pressure (IOP), visual field changes, and surgical outcome. RESULTS The first case describes a 76-year-old woman with orbital amyloidosis who developed gradual unilateral elevation of IOP that was poorly responsive to medical therapy and underwent filtration surgery. Episcleral venous pressure was elevated on the affected side, and histopathologic analysis of the conjunctival tissue confirmed perivascular amyloid deposits, further suggesting raised episcleral venous pressure to be a possible mechanism of glaucoma. The second case describes a 47-year-old white woman with familial amyloid neuropathy with a transthyretin cys-114 mutation. The association of glaucoma with this mutation has not been described previously. Persisting elevation of IOP in one eye was initially responsive to topical antiglaucoma medications but eventually required filtration surgery. Amyloid particles were found in the aqueous and on the lens surface. Histopathologic analysis of the aqueous and sclerectomy specimens demonstrated amyloid, suggesting outflow obstruction as a possible mechanism of glaucoma. Conjunctival buttonholing complicated filtration surgery in both cases, and the leaks eventually resolved with good control of IOP. CONCLUSIONS Amyloid associated with glaucoma may involve different pathophysiologic mechanisms. The elevated IOP may not respond well to medical therapy. Cautious surgical manipulation of the conjunctiva is warranted in these cases.