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Biomedical subjects

Narsing A Rao

Publications and source records attributed to Narsing A Rao.

At least 19 recordsLinked to original sources

Conjunctival epithelium in pars plana vitrectomy specimens.

PURPOSE: To review histopathology of vitrectomy specimens obtained during routine pars plana vitrectomy (PPV) for evidence of inadvertent introduction of conjunctival epithelium into the vitreous cavity during PPV. METHODS: Retrospective review of all vitreous specimens obtained from PPV over a 3-year period during which vitreous samples were routinely submitted from routine and diagnostic PPV. Patient charts and operative reports were reviewed, with particular attention to history of postoperative endophthalmitis, and the use of transconjunctival PPV. RESULTS: A total of 650 specimens were obtained over a 3-year period. Three specimens with conjunctival epithelium were identified. None of these cases resulted in endophthalmitis. Two of these three cases used transconjunctival techniques. In one case all three sclerotomies were made using transconjunctival techniques. CONCLUSIONS: The presence of conjunctiva in the vitreous aspirate from completely transconjunctival PPV indicates that conjunctival epithelium can be inadvertently introduced into the vitreous cavity during PPV. Although none of these cases resulted in endophthalmitis, special care to sterilize the conjunctiva before the creation of transconjunctival sclerotomies is warranted.

Aged↗

Neuroglobin in normal retina and retina from eyes with advanced glaucoma.

BACKGROUND: Neuroglobin is a neurone specific respiratory protein that reversibly binds oxygen. Neuroglobin was discovered in 2000, initially in brain and later, at a 100 times greater concentration, in mouse retina. This protein may be involved in oxygen transport, and/or protection against oxidative stress or premature apoptosis. AIM: To examine the expression of neuroglobin in normal human retina and also in retina from eyes with advanced glaucoma, where hypoxia and ischaemia may be pathological factors. METHODS: Immunofluorescence and electron microscopy were used to examine sections of normal human retina and retina from eyes with end-stage glaucoma. RESULTS: Staining for neuroglobin was present in the plexiform layers and the photoreceptor inner segments in human retina, and increased expression was found to occur in these areas, as well as in the nuclear layers in advanced glaucoma. Much less staining for neuroglobin was present in the other retinal layers. CONCLUSION: Neuroglobin is found in those layers of the human retina that are rich in mitochondria and/or synapses, and consume the highest amount of oxygen. Neuroglobin may be involved in oxygen supply to mitochondria, or in protection from oxidative stress or apoptosis. Neuroglobin expression is increased in advanced glaucoma, and it may protect against hypoxic, ischaemic or oxidative stress, which are thought to be pathological factors that affect the retina in glaucoma.

Aged↗

Differences in clinical findings between Caucasians and African Americans with biopsy-proven sarcoidosis.

OBJECTIVE: To study the prevalence of ocular manifestations in African American and Caucasian patients with biopsy-proven sarcoidosis at the initial ophthalmic examination and to determine the relationship between angiotensin-converting enzyme (ACE) levels, chest x-ray findings, and ocular signs of sarcoidosis. DESIGN: Retrospective, cross-sectional, observational study. PARTICIPANTS: Eighty-one consecutive patients with biopsy-proven sarcoidosis seen at the Doheny Eye Institute from January 1989 through April 2005. METHODS: Medical records were reviewed to obtain demographic data, biopsy site, initial ocular findings, pulmonary symptoms, and results of serum ACE levels and chest x-rays. Associations between ACE level/chest x-ray stages and ocular manifestations related to sarcoidosis were obtained from these data. MAIN OUTCOME MEASURES: Ocular manifestations related to sarcoidosis. RESULTS: Of the 81 patients, 35 were Caucasian; 29 were African American; and the remaining 17 were Hispanic, Asian Indian, and other races. Female patients were older than males (P = 0.05). Sixty-five (80%) of the 81 patients had ocular manifestations related to sarcoidosis. Thirty-three patients (40.7%) had uveitis, 12 (14.8%) had adnexal granulomas, and 25 (30.8%) had keratoconjunctivitis sicca. Of the 33 patients with uveitis, 22 presented with nongranulomatous inflammation. There was no significant association between ocular manifestations related to sarcoidosis and serum ACE levels (P = 0.43) or chest x-ray stage (P>0.99). Of the 29 African American patients, 26 (89.7%) had ocular manifestations related to sarcoidosis, compared with 24 (68.6%) of the 35 Caucasians (P = 0.12). The African American patients were younger (mean age, 44.4 years) than the Caucasian patients (mean age, 52.0) (P = 0.003) and had higher mean ACE levels (P = 0.003). A significantly high proportion of African American males presented with uveitis (P = 0.005), and a significantly high proportion of African American females presented with adnexal granulomas (P = 0.05). CONCLUSIONS: The present study reveals that patients with sarcoidosis can present initially with clinical features of nongranulomatous uveitis. Relative to Caucasians, African American patients with sarcoidosis tend to be younger when they first present to the ophthalmologist and to present with uveitis and/or adnexal granuloma. Serum ACE levels and chest x-ray stages may not help predict the occurrence of ocular changes in sarcoidosis.

Adult↗

Photoreceptor mitochondrial oxidative stress in early experimental autoimmune uveoretinitis.

AIMS: In early S-antigen induced experimental uveitis (EAU), photoreceptor mitochondrial proteins are nitrated prior to macrophage infiltration of the retina, suggesting that oxidative stress is an initial event in the development of EAU. We attempted to detect the oxidative stress and localise it in the EAU retina. METHODS: Lewis rats were immunised with S-antigen in complete Freund's adjuvant (CFA). Animals were injected with CFA alone and non-immunised animals served as controls. Immunised and non-immunised animals were killed on day 5 and subsequent days. Isolated retinas were processed for inducible nitric oxide synthase (iNOS), tumour necrosis factor (TNF)alpha, interferon (IFN)gamma, interleukin (IL)Ialpha and CD28 expression by real time polymerase chain reaction. In addition, iNOS was colocalised with cytochrome c oxidase on day 5 of EAU. Oxidative stress was detected by 2', 7'-dichlorodihydrofluorescein diacetate and localised by a mitochondrial specific marker. Leucocyte and T cell infiltration in the retina/choroid was evaluated by immunohistochemistry. RESULTS: The iNOS, TNFalpha, IFNgamma, IL1alpha and CD28 transcripts were significantly upregulated on day 5 in EAU, and iNOS was colocalised with cytochrome c oxidase in the photoreceptor mitochondria. Oxidative stress was seen primarily in the photoreceptor mitochondria. Occasional T cells were present in the retina at this stage. CONCLUSIONS: During early EAU, mitochondrial oxidative stress is selectively noted in the photoreceptor inner segments. The oxidative stress appears to result from iNOS upregulation in the photoreceptor mitochondria and cytokine generation in the retina by a few antigen specific infiltrating T cells.

Animals↗

Syphilis: reemergence of an old adversary.

OBJECTIVE: To describe the clinical findings in 4 patients with ocular syphilis and to provide a review of the recent rise in syphilis cases in the United States, along with a brief description of current diagnosis and treatment guidelines. DESIGN: Retrospective, observational case series. PARTICIPANTS: Four consecutive patients who presented to our facility during a 6-month interval in 2005 with ocular syphilis. METHODS: Review of clinical, laboratory, photographic, and angiographic records of patients with neurosyphilis who underwent intravenous penicillin G treatment. MAIN OUTCOME MEASURES: Resolution of signs and symptoms of ocular syphilis, including changes in visual acuity. RESULTS: Four patients (3 male: mean age, 46 [range, 39-60 years]; 1 female: age 46 years) demonstrated cerebrospinal fluid findings consistent with neurosyphilis, as evidenced by increased leukocyte counts (>5 white blood cells/mm3), and positive Venereal Disease Research Laboratory or serum fluorescent treponemal antibody absorbed tests. All 4 patients presented with a variety of clinical findings that led to a delay in diagnosis and treatment. Two patients presented with discrete placoid lesions consistent with acute syphilitic posterior placoid chorioretinitis, a manifestation typically observed among the immunocompromised. CONCLUSIONS: Despite a decade of steady decline, syphilis has reemerged in the United States with outbreaks throughout the country in the past few years. Ocular findings, including posterior placoid chorioretinitis, are important diagnostic features in the early treatment of tertiary syphilis and neurosyphilis. Ophthalmologists have the opportunity to play a key role in the early diagnosis and management of this potentially fatal disease.

Adult↗

Sympathetic ophthalmia following postoperative bacterial endophthalmitis: a clinicopathologic study.

PURPOSE: Clinical and histopathologic documentation of sympathetic ophthalmia (SO) development in eyes with postoperative bacterial endophthalmitis. DESIGN: Observational case series; retrospective clinicopathologic study. METHODS: All patients who presented with a clinical diagnosis of SO during 2002 to 2004 were included in the study. The diagnosis of SO was made on the basis of history of penetrating ocular injury, followed by development of bilateral intraocular inflammation, ultrasonographic detection of bilateral diffuse thickening of the choroid, or both. Patients presenting with the additional finding of hypopyon underwent an anterior chamber tap and vitreous aspirate for microbiologic detection of bacteria and fungi. Eight exciting eyes were enucleated and submitted for histologic examination. RESULTS: Of a total of 26 patients with a clinical diagnosis of SO, four also had bacterial endophthalmitis. Of these, histologic examination of three exciting eyes revealed vitreous abscess and typical features of SO. Of the five remaining enucleated globes, histologic examination showed that two eyes had phacoanaphylactic endophthalmitis, and two others revealed features of SO; the one remaining eye had nongranulomatous diffuse choroiditis. CONCLUSIONS: Bacterial endophthalmitis cannot prevent the development of SO. Early diagnosis of coexistent mixed infectious and inflammatory processes, and initiation of antimicrobial treatment directed at the infection followed by immunomodulatory agents to address the autoimmune component may improve the prognosis in such cases.

Abscess↗

Evaluation of the effect on outcomes of the route of administration of corticosteroids in acute Vogt-Koyanagi-Harada disease.

PURPOSE: To compare the effect on outcomes of the route of administration of corticosteroids in acute Vogt-Koyanagi-Harada disease. DESIGN: Retrospective comparative interventional case series. METHODS SETTINGS: Nine international uveitis specialty clinics. STUDY POPULATION: Forty-eight patients presenting over a three-year period to a study center with acute Vogt-Koyanagi-Harada disease. INTERVENTION: Initial treatment with corticosteroid either orally (Oral only group) or intravenously followed by an oral taper (IV+Oral group). MAIN OUTCOME MEASURES: Change in visual acuity with treatment; development of ocular complications, including visually significant cataract, choroidal neovascularization, subretinal fibrosis, fundus pigment migration, nummular hypopigmented lesions, and diffuse fundus depigmentation; use of immunosuppressive therapy. RESULTS: The Oral only group comprised 15 patients (31%) and the IV+Oral group 33 patients (69%). Median follow-up was 15 months. There was no difference in duration of follow-up between groups (P = .234). There was no difference in the change in visual acuity between groups, adjusting for initial visual acuity (P = .402). There were no differences in the rates of development of visually significant cataract, fundus pigmentary changes, or in the rate of use of subsequent immunosuppressive therapy between treatment groups. No patients developed choroidal neovascularization or subretinal fibrosis over the study period. CONCLUSIONS: Route of administration of corticosteroid had no detectable effect on change in visual acuity nor on the development of visually significant complications over the study period. Prospective trials are necessary to address speed of resolution and definitively answer outcome questions.

Acute Disease↗

Ab interno trabeculectomy: development of a novel device (Trabectome) and surgery for open-angle glaucoma.

PURPOSE: To design an instrument to selectively remove trabecular meshwork and Schlemm's canal inner wall (SCIW), and demonstrate its effectiveness by histologic analysis of treated cadaveric human tissue. METHODS: The design parameters of the instrument were the ability to permanently remove a segment of trabecular meshwork and Schlemm's canal inner wall without causing damage to surrounding tissue, and to allow use with standard anterior segment surgical techniques and equipment via an ab interno approach. Treatment was applied to 20 segments of human corneoscleral rims. The treated areas were examined using a confocal microscope and compared with matching areas in untreated controls and simulated goniotomy. RESULTS: The resultant instrument system surgically removes the trabecular meshwork and Schlemm's canal inner wall from an anterior chamber approach. It consists of a disposable surgical handpiece with irrigation, aspiration, and electrocautery to focally ablate the target tissues. The attached console includes a high-frequency (550 KHz) electrosurgical generator and irrigation/aspiration controlled by a foot pedal. Histologic examination of specimens treated with the Trabectome displayed disruption of the trabecular meshwork and Schlemm's canal inner wall without damage to surrounding structures. The specimens treated by simulated goniotomy displayed significant damage to the outer wall of Schlemm's canal and the surrounding sclera. The controls showed no disruption or damage to any tissues. CONCLUSIONS: The Trabectome system is designed for performing trabeculectomy via an ab interno approach. It successfully removed sections of trabecular meshwork and Schlemm's canal inner wall with less injury to the adjacent tissue compared with goniotomy knife in vitro. Theoretically, this procedure should provide direct access of aqueous humor to Schlemm's canal.

Adolescent↗

Retinal microglial activation and chemotaxis by docosahexaenoic acid hydroperoxide.

PURPOSE: Peroxynitrite generated during the early phase of experimental autoimmune uveoretinitis (EAU) causes peroxidation of docosahexaenoic acid (22:6), a principal unsaturated fatty acid of the photoreceptor membrane, to its hydroperoxide (22:6HP). During this phase, microglia migrate to the site of photoreceptors. The effect of 22:6HP on the migration of isolated retinal microglia was investigated. METHODS: Retinal microglia were isolated and cultured from newborn Lewis rats and identified immunohistochemically by OX42 antibody staining. Chemotactic activity of the microglia toward 22:6HP was assayed and compared with 22:6 and other control cultures. The effect of 22:6HP on the organization of actin fibers and on the expression of Rac and Iba1 in the microglia was studied by confocal microscopy. The gene and protein expression of Rac and Iba1 in these microglia was analyzed by real-time PCR and Western blot. RESULTS: Ninety-five percent of isolated microglia stained for OX42 and a chemotactic assay showed that 22:6HP was a potent chemoattractant for these cells. Exposure to hydroperoxide resulted in reorganization of F-actin with intense staining within the lamellipodia. Iba1 and Rac were upregulated in these activated cells and localized in the cell periphery and the lamellipodia. CONCLUSIONS: 22:6HP can activate retinal microglia and is a potent chemoattractant for microglial migration in response to the activation of Rac and reorganization of actin cytoskeleton. In EAU, microglial migration toward the photoreceptors may be mediated by 22:6HP formed in the photoreceptors, and these migrating cells could help modulate the inflammation.

Actins↗

Atypical presentation of multiple evanescent white dot syndrome involving granular lesions of varying size.

PURPOSE: To report an atypical presentation of multiple evanescent white dot syndrome (MEWDS). DESIGN: Observational case report. METHODS: Review of the clinical, laboratory, photographic, and angiographic records of a patient with MEWDS. RESULTS: A 29-year-old woman presented with 20/400 vision in the right eye associated with multiple, granular lesions of varying sizes (100-1000 microm) in the outer retina, a prominent panuveitis, diffuse choroidal thickening and enlarged blindspot. The multiple lesions and visual disturbances resolved within 4 weeks with corticosteroid treatment, and the patient was diagnosed with MEWDS. CONCLUSIONS: Clinicians should be aware of atypical manifestations of MEWDS. The patient's unusual fundoscopic changes and prominent intraocular inflammatory reaction are findings that have not been reported in patients with MEWDS.

Adult↗

Splendore-Hoeppli phenomenon in the conjunctiva: immunohistochemical analysis.

PURPOSE: To present two cases of conjunctival lesions exhibiting the Splendore-Hoeppli phenomenon, each with different immunohistochemical findings. DESIGN: Interventional case reports. METHODS: Two young males with conjunctival lesions underwent biopsy. Demographic data and timing of biopsy were extracted from the charts. The biopsy specimens were formalin fixed and paraffin embedded for light microscopy. Immunohistochemical staining using the peroxidase method was carried out on each for IgG, IgM, IgA, the C3 component of complement, and eosinophilic major basic protein. MAIN OUTCOME MEASURES: Presence of positive or negative staining for the various antigens. RESULTS: Both biopsy specimens exhibited the Splendore-Hoeppli phenomenon, a morphologically unique process consisting of an amorphous, eosinophilic material surrounded by epithelioid histiocytes, multinucleated giant cells, lymphocytes, and eosinophils. Two staining patterns were seen. One revealed predominately immunoglobulin deposition, whereas the other revealed primarily eosinophilic major basic protein. This is the first instance we are aware of in which eosinophilic major basic protein was the predominate finding in an ocular specimen. CONCLUSION: The composition of Splendore-Hoeppli phenomenon material varies and may be related to various factors, including timing of biopsy and prior treatment.

Adult↗

Vogt-Koyanagi-Harada disease in patients with chronic hepatitis C.

PURPOSE: To report the cases of four patients with hepatitis C virus infection who experienced clinical features that are virtually identical to Vogt-Koyanagi-Harada disease (VKH). DESIGN: Retrospective observational case series. METHODS: Medical records of patients who were referred between January and December 2003 were reviewed for diagnosis and management of VKH and who also had chronic hepatitis C virus (HCV) infection. RESULTS: Four white patients had the clinical features of VKH. Three of the patients experienced intraocular inflammation while they were being treated for HCV infection with pegylated interferon alpha 2b and ribavirin. The intraocular inflammation responded to systemic corticosteroid treatment and to discontinuation of antiviral agents. CONCLUSION: Although the number of patients who were studied is limited, there appears to be an association between HCV infection that was treated with pegylated interferon alpha 2b and the development of VKH-like disease. Further studies are required to confirm such an association.

Adult↗

Initial evaluation of subcutaneous daclizumab treatments for noninfectious uveitis: a multicenter noncomparative interventional case series.

PURPOSE: To assess the feasibility of a study design that may determine whether subcutaneous administration of the interleukin-2 receptor antibody daclizumab can safely reduce the dependence on standard systemic corticosteroids or other immunosuppressive regimens in patients with sight-threatening, noninfectious intermediate uveitis, posterior uveitis, or panuveitis. DESIGN: Prospective, multicenter, nonrandomized, noncomparative, open-label interventional trial. PARTICIPANTS: Fifteen patients, 5 each at 3 clinical centers, with noninfectious intermediate, posterior, or panuveitis, who require a currently stable immunosuppression regimen of systemic corticosteroids and/or other systemic treatments to control noninfectious intraocular inflammation. METHODS: After enrollment and baseline ophthalmic evaluations, 2 induction treatments were given 2 weeks apart using subcutaneous (SC) daclizumab at 2 mg/kg. Subcutaneous daclizumab maintenance treatments were then continued every 2 weeks at 1 mg/kg for 6 months. The initial immunosuppression load was tapered over 8 to 12 weeks in a staggered fashion beginning with the first induction treatment. Safety evaluations were performed at each treatment visit, with a primary efficacy evaluation at 12 weeks and a repeat efficacy evaluation at 26 weeks. MAIN OUTCOME MEASURES: Best-corrected visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] method) with a concurrent taper of concomitant systemic immunosuppression medication load (tabulated by use of a weighted scoring system) was assessed; target for success was defined as a 50% or greater reduction in concomitant immunosuppression load by 12 weeks while maintaining visual acuity within 5 ETDRS letters of baseline. Ocular inflammation was assessed at each visit with standardized grading scales. RESULTS: Ten of 15 patients (67%) receiving SC daclizumab treatments every other week successfully achieved the primary efficacy end point of reducing their concomitant immunosuppression load by at least 50% while maintaining their baseline visual acuity at 12 and 26 weeks. Subcutaneous daclizumab injections were well tolerated with no serious adverse events observed during the 6 months of treatments, although 3 patients experienced possibly related, nonserious adverse events. CONCLUSIONS: Subcutaneous daclizumab induction treatments at 2 mg/kg followed by 1 mg/kg maintenance treatments every other week seems safe and, in most cases, may reduce the concomitant immunosuppressive load required to treat noninfectious uveitis for 12 to 26 weeks.

Adolescent↗