Search

Purpose To determine classification criteria for Vogt-Koyanagi-Harada (VKH) disease Design Machine learning of cases with VKH disease and 5 other panuveitides. Methods Cases of panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the panuveitides. The resulting criteria were evaluated on the validation set. Results One thousand twelve cases of panuveitides, including 156 cases of early-stage VKH and 103 cases of late-stage VKH, were evaluated. Overall accuracy for panuveitides was 96.3% in the training set and 94.0% in the validation set (95% confidence interval 89.0, 96.8). Key criteria for early-stage VKH included: 1) exudative retinal detachment with characteristic appearance on fluorescein angiogram or optical coherence tomography or 2) panuveitis with ≥2 of 5 neurologic symptoms/signs. Key criteria for late-stage VKH included history of early-stage VKH and either: 1) sunset glow fundus or 2) uveitis and ≥1 of 3 cutaneous signs. The misclassification rates in the learning and validation sets for early-stage VKH were 8.0% and 7.7%, respectively, and for late-stage VKH 1.0% and 12%, respectively. Conclusions The criteria for VKH had a reasonably low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Purpose To determine classification criteria for multifocal choroiditis with panuveitis (MFCPU) DESIGN: : Machine learning of cases with MFCPU and 8 other posterior uveitides. Methods Cases of posterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the posterior uveitides. The resulting criteria were evaluated on the validation set. Results One thousand sixty-eight cases of posterior uveitides, including 138 cases of MFCPU, were evaluated by machine learning. Key criteria for MFCPU included: 1) multifocal choroiditis with the predominant lesions size >125 µm in diameter; 2) lesions outside the posterior pole (with or without posterior involvement); and either 3) punched-out atrophic chorioretinal scars or 4) more than minimal mild anterior chamber and/or vitreous inflammation. Overall accuracy for posterior uveitides was 93.9% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for MFCPU were 15% in the training set and 0% in the validation set. Conclusions The criteria for MFCPU had a reasonably low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Purpose To determine classification criteria for Behcet disease uveitis. Design Machine learning of cases with Behcet disease and 5 other panuveitides. Methods Cases of panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation set. Results One thousand twelve of cases panuveitides, including 194 cases of Behcet disease with uveitis, were evaluated by machine learning. The overall accuracy for panuveitides was 96.3% in the training set and 94.0% in the validation set (95% confidence interval 89.0, 96.8). Key criteria for Behcet disease uveitis were a diagnosis of Behcet disease using the International Study Group for Behcet Disease criteria and a compatible uveitis, including: 1) anterior uveitis; 2) anterior chamber and vitreous inflammation; 3) posterior uveitis with retinal vasculitis and/or focal infiltrates; or 4) panuveitis with retinal vasculitis and/or focal infiltrates. The misclassification rates for Behcet disease uveitis were 0.6 % in the training set and 0% in the validation set, respectively. Conclusions The criteria for Behcet disease uveitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Purpose To determine classification criteria for birdshot chorioretinitis. Design Machine learning of cases with birdshot chorioretinitis and 8 other posterior uveitides. Methods Cases of posterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior/panuveitides. The resulting criteria were evaluated on the validation set. Results One thousand sixty-eight cases of posterior uveitides, including 207 cases of birdshot chorioretinitis, were evaluated by machine learning. Key criteria for birdshot chorioretinitis included a multifocal choroiditis with: 1) the characteristic appearance a bilateral multifocal choroiditis with cream-colored or yellow-orange, oval or round choroidal spots ("birdshot" spots); 2) absent to mild anterior chamber inflammation; and 3) absent to moderate vitreous inflammation; or multifocal choroiditis with positive HLA-A29 testing and either: 1) classic "birdshot spots" or 2) characteristic imaging on indocyanine green angiography. Overall accuracy for posterior uveitides was 93.9% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for birdshot chorioretinitis were 10% in the training set and 0% in the validation set. Conclusions The criteria for birdshot chorioretinitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

PURPOSE: To determine classification criteria for sympathetic ophthalmia DESIGN: Machine learning of cases with sympathetic ophthalmia and 5 other panuveitides. METHODS: Cases of panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the panuveitides. The resulting criteria were evaluated on the validation set. RESULTS: One thousand twelve cases of panuveitides, including 110 cases of sympathetic ophthalmia, were evaluated by machine learning. The overall accuracy for panuveitides was 96.3% in the training set and 94.0% in the validation set (95% confidence interval 89.0, 96.8). Key criteria for sympathetic ophthalmia included bilateral uveitis with 1) a history of unilateral ocular trauma or surgery and 2) an anterior chamber and vitreous inflammation or a panuveitis with choroidal involvement. The misclassification rates for sympathetic ophthalmia were 4.2 % in the training set and 6.7% in the validation set, respectively. CONCLUSIONS: The criteria for sympathetic ophthalmia had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research. PRECIS: Using a formalized approach to developing classification criteria, including informatics-based case collection, consensus-technique-based case selection, and machine learning, classification criteria for sympathetic ophthalmia were developed. Key criteria included bilateral uveitis with a history of unilateral ocular trauma or surgery and either anterior chamber and vitreous inflammation or panuveitis with choroidal involvement. The resulting criteria had a low misclassification rate.

Purpose : To determine classification criteria for intermediate uveitis, non-pars planitis type (IU- NPP, also known as undifferentiated intermediate uveitis) Design : Machine learning of cases with IU-NPP and 4 other intermediate uveitides. Methods : Cases of intermediate uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation set. Results : Five hundred eighty-nine of cases of intermediate uveitides, including 114 cases of IU-NPP, were evaluated by machine learning. The overall accuracy for intermediate uveitides was 99.8% in the training set and 99.3% in the validation set (95% confidence interval 96.1, 99.9). Key criteria for IU-NPP included unilateral or bilateral intermediate uveitis with neither 1) snowballs in the vitreous nor 2) snowbanks on the pars plana. Other key exclusions included: 1) multiple sclerosis, 2) sarcoidosis, and 3) syphilis. The misclassification rates for pars planitis were 0 % in the training set and 0% in the validation set, respectively. Conclusions : The criteria for IU-NPP had a low misclassification rate and appeared to perform well enough for use in clinical and translational research.

T cells are intimately involved in noninfectious autoimmune uveitis, and their inhibition has been shown in both experimental models and human disease to be beneficial in controlling ocular inflammation. Two categories of T cell inhibitors exist, the calcineurin inhibitors, consisting of cyclosporine and tacrolimus, and the mammalian target of rapamycin (mTOR) inhibitors, consisting of sirolimus (also known as rapamycin) and everolimus. All are available as oral formulations, and, in addition, sirolimus is under study as a locally administered agent. All four compounds are metabolized by the cytochrome P450 enzyme system and therefore have the potential for significant drug-drug interactions. In addition, sometimes serious side effects can develop, including systemic hypertension and nephrotoxicity that require tight monitoring. Despite these limitations, the T cell inhibitors provide a useful addition to the uveitis treatment armamentarium.

Importance The prevalence of irreversible vision impairment in the United States is expected to increase by 2050. Vision rehabilitation is the primary treatment option. Clinical trials have established its efficacy in improving quality of life. Yet studies indicate that patients experience many barriers to accessing low-vision care. Objectives To examine the rate of referral for low-vision rehabilitation services by resident and attending ophthalmologists for adults with irreversible vision impairment and to assess the knowledge, attitudes, and beliefs of patients about vision rehabilitation. Design, Setting, and Participants Cross-sectional study with enrollment from June 20, 2016, to January 31, 2017, of 143 adults 18 years or older seen in a publicly funded, comprehensive eye clinic in Jefferson County, Alabama, and having 1 or both eyes with irreversible vision impairment (visual acuity was defined as 20/60 or worse) per the electronic health record. Exposures Demographic characteristics; patient questionnaire on knowledge, attitudes, and beliefs about vision rehabilitation; general cognitive status (Short Orientation-Memory-Concentration test); depressive symptoms (Patient Health Questionnaire-9); health literacy (Rapid Estimate of Adult Literacy in Medicine, Revised [REALM-R]); and self-reported difficulty in everyday activities. Main Outcomes and Measures Proportion of patients with irreversible vision impairment who were referred by ophthalmologists to low-vision rehabilitation services per the electronic health record. Results Of 143 patients enrolled with irreversible vision impairment in 1 or both eyes, the mean (SD) age was 55.4 (11.1) years and 68 (47.6%) were women. Most patients were African American (123 [86.0%]), uninsured (88 [61.5%]), and unemployed (92 [64.3%]); on average, they had normal cognitive status, minor depressive symptoms, and limited health literacy. As noted in the electronic health record, the rate of referral for low-vision rehabilitation services was 11.4% for patients with irreversible bilateral vision impairment (4 of 35 patients) and 1.9% for those with unilateral impairment (2 of 108). Most patients with bilateral (31 of 34 [91.2%]) and unilateral (90 of 97 [92.8%]) impairment indicated that they were bothered by their vision impairment, and most reported difficulty with reading (33 of 34 patients [97.1%] who were bilaterally impaired vs 85 of 104 [81.7%] who were unilaterally impaired). Conclusions and Relevance Results of this study suggest a need to better educate ophthalmologists and residents in ophthalmology about referrals to low-vision rehabilitation services for patients with irreversible vision impairment.

Purpose: Extracellular deposits containing hydroxyapatite, lipids, proteins, and trace metals that form between the basal lamina of the RPE and the inner collagenous layer of Bruch's membrane are hallmarks of early AMD. We examined whether cultured RPE cells could produce extracellular deposits containing all of these molecular components.Methods: Retinal pigment epithelium cells isolated from freshly enucleated porcine eyes were cultured on Transwell membranes for up to 6 months. Deposit composition and structure were characterized using light, fluorescence, and electron microscopy; synchrotron x-ray diffraction and x-ray fluorescence; secondary ion mass spectroscopy; and immunohistochemistry.Results: Apparently functional primary RPE cells, when cultured on 10-μm-thick inserts with 0.4-μm-diameter pores, can produce sub-RPE deposits that contain hydroxyapatite, lipids, proteins, and trace elements, without outer segment supplementation, by 12 weeks.Conclusions: The data suggest that sub-RPE deposit formation is initiated, and probably regulated, by the RPE, as well as the loss of permeability of the Bruch's membrane and choriocapillaris complex associated with age and early AMD. This cell culture model of early AMD lesions provides a novel system for testing new therapeutic interventions against sub-RPE deposit formation, an event occurring well in advance of the onset of vision loss.

Purpose To assess the current burden of ocular toxocariasis (OT) and to gain knowledge regarding the diagnostic and treatment practices used in the ophthalmologic community in the United States. Design Web-based, cross-sectional survey. Participants Subspecialty ophthalmologists who are currently practicing in the United States. Methods An electronic survey was sent to 3020 ophthalmologic subspecialists belonging to the American Uveitis Society (AUS), the American Society of Retina Specialists (ASRS), or the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) to capture demographic, clinical, diagnostic, and treatment data on patients with OT seen in their practices between September 2009 and September 2010. Main Outcome Measures The demographic, epidemiologic, and clinical characteristics of each reported patient with OT. Results A total of 159 patients with OT were reported by 559 respondents (19%). The median patient age was 11.5 years (range, 1–66 years). Seventy-two patients (45%) with OT lived in the Southern region of the United States. Thirty-one (69%) of 45 patients with OT owned a dog or cat. Vision loss was reported in 46 (85%) of 54 patients with OT; 32 (71%) of 45 patients had permanent vision loss, 13 patients (29%) had temporary vision loss, and duration of vision loss was unreported for 1 patient. Of the 32 patients with OT with permanent vision loss, 30 (94%) had a subretinal granulomatous mass/scar, peripheral granuloma with traction bands, or posterior pole granuloma noted on ophthalmologic examination. Subretinal granulomatous mass/scar, vitritis, and scotoma were the most common ophthalmologic signs found on examination of patients with OT. Conclusions Ocular toxocariasis continues to occur in the United States, where it affects mainly children and causes permanent vision loss in many patients. Healthcare professionals should counsel patients and their family members about prevention strategies in an effort to decrease infection rates and morbidity due to Toxocara . Further improvement of diagnostic and treatment tools is needed to assist ophthalmologists in treating patients with OT. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose We sought to characterize the long-term outcomes and complications of subconjunctival triamcinolone acetonide injection (STI) for non-necrotizing, noninfectious anterior scleritis. Design Retrospective, interventional, noncomparative, multicenter study. Participants Sixty-eight eyes of 53 patients from 9 participating hospitals in the United States, Singapore, and Australia. Only eyes with 6 or more months of follow-up were included. Intervention Subconjunctival injection of 2 to 8 mg of triamcinolone acetonide was administered to eyes with non-necrotizing, noninfectious anterior scleritis. Main Outcome Measures Resolution of signs and symptoms, time to recurrence of scleritis, and side effect profile. Results Median follow-up was 2.3 years (range, 6 months to 8.3 years). Sixty-six eyes (97.0%) experienced improvement of signs and symptoms after 1 injection. Twenty-four months after a single injection, 67.6% of eyes remained recurrence-free, whereas at 48 months, 50.2% were recurrence-free. Some 55.0% of patients who had adverse effects from systemic medications were off all systemic medications at last follow-up; 55.0% of patients who were taking systemic medications at the time of first triamcinolone acetonide injection were not taking prednisone and immunosuppressants at this time; 76.2% of patients still requiring systemic agents had associated systemic disease. Fourteen eyes (20.6%) had ocular hypertension not requiring intraocular pressure (IOP)-lowering therapy. Two eyes (2.9%) were treated with topical IOP-lowering agents alone, and 2 eyes required surgical intervention for glaucoma. None developed scleral necrosis or melt. Conclusions This retrospective, international study carried out at 9 hospitals suggests that STI can treat non-necrotizing, noninfectious anterior scleritis with side effects limited to elevated IOP in a few patients. Although no cases of scleral melt or necrosis were observed, we cannot definitively conclude that this may not occur after STI. Intraocular pressure should be closely monitored after STI. Subconjunctival triamcinolone acetonide injection may be useful as adjuvant therapy or to decrease systemic medication burden. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

In geographic atrophy (GA), the non-neovascular end stage of age-related macular degeneration (AMD), the macular retinal pigment epithelium (RPE) progressively degenerates. Membrane cofactor protein (MCP, CD46) is the only membrane-bound regulator of complement expressed on the human RPE basolateral surface. Based on evidence of the role of complement in AMD, we hypothesized that altered CD46 expression on the RPE would be associated with GA development and/or progression. Here we report the timeline of CD46 protein expression changes across the GA transition zone, relative to control eyes, and relative to events in other chorioretinal layers. Eleven donor eyes (mean age 87.0 ± 4.1 yr) with GA and 5 control eyes (mean age 84.0 ± 8.9 yr) without GA were evaluated. Macular cryosections were stained with PASH for basal deposits, von Kossa for calcium, and for CD46 immunoreactivity. Internal controls for protein expression were provided by an independent basolateral protein, monocarboxylate transporter 3 (MCT3) and an apical protein, ezrin. Within zones defined by 8 different semi-quantitative grades of RPE morphology, we determined the location and intensity of immunoreactivity, outer segment length, and Bruch's membrane calcification. Differences between GA and control eyes and between milder and more severe RPE stages in GA eyes were assessed statistically. Increasing grades of RPE degeneration were associated with progressive loss of polarity and loss of intensity of staining of CD46, beginning with the stages that are considered normal aging (grades 0-1). Those GA stages with affected CD46 immunoreactivity exhibited basal laminar deposit, still-normal photoreceptors, and concomitant changes in control protein expression. Activated or anteriorly migrated RPE (grades 2-3) exhibited greatly diminished CD46. Changes in RPE CD46 expression thus occur early in GA, before there is evidence of morphological RPE change. At later stages of degeneration, CD46 alterations occur within a context of altered RPE polarity. These changes precede degeneration of the overlying retina and suggest that therapeutic interventions be targeted to the RPE.

Purpose To report on the presentation and treatment of a patient with infectious posterior segment uveitis because of infection with Rickettsia rickettsii. Methods Interventional case report. We conducted a retrospective chart review of a 39-year-old man who presented with a history of acute vision loss in his right eye over a 6-day period. Vision at presentation in the involved eye was 2/200, with mild conjunctival injection, trace anterior chamber cell, moderate vitritis, localized retinitis and retinal hemorrhages, and severe macular edema. The left eye had 20/20 vision and was normal on examination. History was notable for a tick bite followed by high fevers, 1 month before presentation, at which time his family physician diagnosed mononucleosis syndrome with low platelets. Results A serum Rickettsia rickettsii test was positive. He was treated with oral doxycycline followed by corticosteroids. Vision gradually improved to 20/20 with minimal residual metamorphopsia. Conclusion Only ten cases of Rocky Mountain spotted fever-related uveitis have been reported. The current case is unique because of the delayed onset of ophthalmic complications after the tick bite, its unilateral nature, dramatic improvement in acuity after treatment, and lack of associated rash.

To characterize the distribution of membrane-bound components of the complement system in normal human retina, eyes from eight human donors with no history of ocular disease, ranging in age from 47 to 85 years were examined using immunohistochemistry to localize the C3a receptor (C3aR), C5a receptor (C5aR), CD46, CD55, and CD59 in cryosections prepared from donor posterior segments. The C3aR was identified in the nerve fiber layer in a sawtooth-patterned band. Vimentin, used as a Müller cell marker, produced a similar staining pattern. The C5aR was detected on specific rounded structures in the inner plexiform layer and occasionally in the nerve fiber layer. CD46 produced markedly specific staining of the basolateral surface of the retinal pigment epithelium. CD55 was localized to the nerve fiber layer. Staining for these proteins was consistent across all eyes studied. CD59 was expressed throughout the nerve fiber layer and labeled vessels that extended through the ganglion cell, inner plexiform, and inner nuclear layers, but this pattern was only confirmable in a single subject. Complement anaphylatoxin receptors and regulatory proteins are localized in different but internally consistent patterns in normal adult human retina, independent of the age of the donor. C3aR and C5aR localization only in the inner retina contrasts with previously reported findings in the central nervous system of wide spread diffuse staining. The complement regulators CD55 and CD59 were found primarily on the inner retina, while CD46 was present exclusively in a polarized fashion on the RPE.

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.

Uveitis is a leading cause of blindness affecting individuals of all ages, genders, and races. Uveitis may be due to autoimmune, infectious, toxic, malignant, or traumatic processes. Some evidence supports an association between conditions previously presumed to be autoimmune and viral infectious agents. For autoimmune uveitis, therapy is nonspecific, typically beginning with corticosteroids. For nonresponsive disease or for corticosteroid sparing, recent reports on mycophenolate mofetil, infliximab, and interferon therapy show success for various forms of uveitis. Treatment of the complications of uveitis, especially cystoid macular edema, is difficult. Vitamin E appears to offer little benefit, whereas octreotide may be effective. Recent collaborative efforts at standardization in the field should enhance studies on these conditions.

In this report, we describe the effect of complement deficiency and inhibition on experimental autoimmune uveoretinitis (EAU). C57BL/6 mice genetically deficient in C3 (C3-/-) or expressing a soluble complement activation inhibitor (soluble complement receptor related protein Y or sCrry) in a CNS-targeted fashion, (sCrry/GFAP) were induced for EAU via peripheral immunisation with a peptide of amino acids 1-20 of human interphotoreceptor retinoid binding protein in complete Freund's adjuvant with concurrent intraperitoneal pertussis toxin. The incidence and severity of EAU in the mutant mice was compared with that in simultaneously induced C57BL/6 wild type mice. The sCrry protein was detected in retinal extracts from transgenic but not wild type mice by western blot. C3-/- mice had a significant reduction in the incidence of EAU compared with wild type mice (incidence 44 versus 89%, respectively, p=0.0417) and a significant reduction in the severity of EAU (median disease score values 0 versus 1.3, respectively, p=0.0253). Similarly, sCrry mice had a significant reduction in the incidence of EAU compared with wild type mice (incidence 57 versus 100% respectively, p=0.0033) and a significant reduction in the severity of EAU (median disease score values 0.18 versus 1.85, respectively, p=0.0054). A genetic deficiency of C3 and production of a soluble complement inhibitor targeted to the CNS and eye are protective against EAU.

Purpose Subconjunctival corticosteroid injection (SCI) for nonnecrotizing anterior scleritis remains controversial, partly because long-term follow-up is not available. This study documents the efficacy and adverse effects of SCI. Design Retrospective, noncomparative, interventional case series. Participants Thirty-eight eyes of 35 patients with nonnecrotizing, noninfectious anterior scleritis resistant to prior systemic or local therapy. Intervention Subconjunctival triamcinolone acetonide injection. Main Outcome Measure Persistence or resolution of signs and symptoms of anterior scleritis and development of complications. Results Thirty-six of 38 eyes had complete resolution of signs and symptoms within 6 weeks of SCI. Fifteen eyes had follow-up of ≥30 months. There were no instances of scleral melting or perforation; adverse events included subconjunctival hemorrhage (5 patients), transient ocular hypertension without evidence of glaucoma (4 patients), cataract (2 patients), and glaucoma (2 patients). Subconjunctival corticosteroid injection resulted in reduced dependence on systemic medications. Conclusion Subconjunctival corticosteroid injection in eyes that failed other therapies is effective, reduces dependence on systemic medications, and did not result in scleral necrosis over a median follow-up period of 29 months.

To determine if complement anaphylatoxin-mediated inflammation contributes to the development and progression of experimental autoimmune uveitis (EAU), we induced disease in wild type and complement anaphylatoxin receptor-deficient mice (C3a receptor −/− , C5a receptor −/− and C3aR −/− /C5aR −/− ) and evaluated the eyes three weeks post-induction. No differences in disease severity or in disease incidence were seen between wild type controls and anaphylatoxin receptor-deficient mice. Our data indicate that C3a and C5a-mediated functions are not critical to the development of EAU.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease, the exact etiology of which is unknown. It is characterized by the production of pathological autoantibodies which adhere to cellular surfaces or form immune complexes which deposit in tissue, leading to end-organ damage via inflammatory mechanisms including complement activation. SLE may manifest itself in any organ system. In the eye, keratoconjunctivitis sicca is the most common finding. Other ophthalmic sites of involvement include the cornea, conjunctiva, episclera, sclera, uveal tract, retina, vasculature, optic nerve, and orbit. Therapy varies based on the disease manifestation and severity.

Purpose Intraocular pressure is a risk factor for the development of glaucomatous optic neuropathy. With few exceptions, higher mean intraocular pressure and greater prevalences of glaucoma have been reported for individuals of African origin. This study was performed to compare the mean intraocular pressure of a group of ethnic East Africans living in the United States with that of Caucasians living in the same community. Patients and methods Retrospective comparison of Somali patients 30 years of age or greater with age- and gender-matched Caucasian control subjects. All patients were seen in the same clinic in Seattle, Washington, between July 1996 and March 1998. Patients were excluded for conditions or medications affecting intraocular pressure and for a diagnosis of glaucoma. Mean intraocular pressure of the two populations was compared using an independent sample two-tailed t test. Results Following exclusions and defined age limits, 57 Somali patients and 57 Caucasian control subjects were included in the final analysis. Mean age of Somalis was 48.5 +/- 12.2 years versus 48.1 +/- 11.3 years for control subjects (P = 0.84). The mean intraocular pressure of Somalis was 13.76 +/- 3.63 mm Hg versus 13.94 +/- 2.78 mm Hg for control subjects (P = 0.77). Conclusion Some populations of African origin may not have higher mean intraocular pressures compared with non-African populations. Consideration of ethnic and racial origins more specific than "African" should be given when evaluating intraocular pressure in individual patients.

We evaluated the role of extracellular UTP and other nucleotides in the regulation of chloride (JCl) and fluid secretion (JCl) across the pigmented rabbit conjunctiva. Jv was determined in freshly excised conjunctival tissues mounted between two buffer reservoirs maintained in an enclosed environment at 37 degrees C. Short circuit current (Isc) and 36Cl flux were measured using modified Ussing-type chambers. Fluid flux measurements were made with a pair of capacitance probes. After observing the baseline for 15 to 30 min, fluid flux was measured in the presence of mucosally applied nucleotides (10 microM) for a period of 30 min. Mucosal application of 10 microM each of UTP, UDP, ATP, ADP, AMP, adenosine, and ATP-gamma-S transiently stimulated fluid secretion across the conjunctiva to a significant extent for 10 to 15 min. Other nucleotides did not show any significant effect. The stimulation of fluid secretion correlated well with the stimulation in Isc (r2 = 0.85). UTP (0.1-1000 microM) led to a maximal increase in fluid secretion by 11.72 +/- 0.48 microl/(h x cm2) with an EC50 value of 10.39 +/- 1.08 microM. ATP (0.1-1000 microM) caused a maximal increase in fluid secretion by 11.89 +/- 0.88 microl/(h x cm2) with an EC50 value of 17.23 +/- 2.63 microM. Adenovirus type 5 (Ad5) infection significantly decreased both net 36Cl secretion across the conjunctiva by approximately 56% and the rate of fluid secretion by approximately 56%. UTP (10 microM), but not 1 mM 8-bromo-cAMP, was able to elicit a normal stimulatory response in the Ad5-infected tissues. In conclusion, mucosal application of purinergic nucleotides may be therapeutically important in restoring ion and fluid secretion in the diseased conjunctiva.

Purpose To describe the ocular presentation of disseminated mycobacterial disease occurring during immune-recovery in a patient with acquired immune deficiency syndrome (AIDS). Study design Case report and literature review. Participants A 41-year-old AIDS patient with a prior diagnosis of cytomegalovirus retinitis. Methods The patient developed progressive, bilateral multifocal choroiditis with panuveitis 2 months after beginning and responding to highly active antiretroviral therapy. His left eye became blind and painful and was enucleated. Pathologic examination revealed massive choroiditis with well-formed, discrete granulomas and multiple intracellular and extracellular acid-fast organisms within the choroidal granulomas. Culture and polymerase chain reaction of vitreous specimens revealed Mycobacterium avium complex (MAC). Results Empiric, and later sensitivity-guided, local and systemic antibiotic therapy was used to treat the remaining right eye, but it continued to deteriorate. Despite medical therapy, three vitrectomies and repeated intravitreal injections of amikacin, a total retinal detachment ensued. One week after the third vitrectomy, the patient died from mesenteric artery thrombosis in the setting of disseminated mycobacterial disease. Conclusions This is the first report of ocular inflammation as the presenting finding in the recently recognized syndrome of immune-recovery MAC disease. Pathogenesis of this entity is related to an enhanced immune response to a prior, subclinical, disseminated infection. The formation of discrete granulomas, normally absent in MAC infections in AIDS, reflects this mechanism.

Vogt-Koyanagi-Harada disease is a chronic, granulomatous systemic autoimmune disease with manifestations in the ocular, central nervous, auditory, and integumentary systems. The target of attack seems to be antigens associated with melanocytes. Patients are usually of Asian, Middle Eastern, Asian Indian, Native American, or Hispanic ethnicity, and complain of neurologic symptoms quickly followed by decreased vision caused by a choroiditis, frequently with exudative retinal detachments. Corticosteroids are the mainstay of therapy, but other immunosuppressive therapy may be required. Complications, including cataract, glaucoma, choroidal neovascular membrane formation, and subretinal fibrosis, may limit final visual acuity.

Purpose Prospective evaluation of the efficacy and safety of subconjunctival triamcinolone injections for resistant, nonnecrotizing, anterior scleritis. Design Prospective, noncomparative, interventional case series. Participants Twelve eyes of 10 consecutive patients seen in the Doheny Eye Institute between August 1999 and December 2000 with diffuse, nonnecrotizing anterior scleritis that was resistant to systemic antiinflammatory therapy. Eyes with a history of steroid response were excluded. Intervention Subconjunctival injection of triamcinolone acetonide to the areas of maximal inflammation. Main outcome measures Scleritis activity, adverse treatment effects, and number of systemic medications required at the end of the follow-up period. Results Within 1 to 14 days after injection, complete resolution of signs and symptoms was achieved in 11 eyes and partial resolution in 1 eye. Two patients had one recurrence each, 2.5 and 11 months after injection. Six of 10 patients were able to discontinue all systemic therapy (prednisone ± immunosuppressive drugs); the remaining 4 needed continued oral therapy for systemic indications. Transient ocular hypertension and subconjunctival hemorrhage occurred in one eye each. Median follow-up period was 15 months. No eye developed necrotizing scleritis. Conclusions Subconjunctival injection of triamcinolone acetonide is a safe and effective treatment for resistant, nonnecrotizing anterior scleritis. It provides rapid effect, is well tolerated, and may spare patients the significant complications and side effects of systemic corticosteroid and immunosuppressive therapy.

PURPOSE: To present revised criteria for the diagnosis of Vogt-Koyanagi-Harada disease, a chronic, bilateral, granulomatous ocular and multisystem inflammatory condition of unknown cause. METHODS: Diagnostic criteria and nomenclature were subjects of discussion at the First International Workshop on Vogt-Koyanagi-Harada Disease on October 19–21, 1999, at the University of California, Los Angeles, Conference Center, Lake Arrowhead, California. A committee appointed by the workshop participants was charged with drafting revised criteria for Vogt-Koyanagi-Harada disease, based on discussions held during the conference. This article is the consensus committee report. RESULTS: New criteria, taking into account the multisystem nature of Vogt-Koyanagi-Harada disease, with allowance for the different ocular findings present in the early and late stages of the disease, were formulated and agreed upon by the committee. These criteria are based on additional knowledge and experience of experts in the field and are believed to reflect disease features more fully than previously published criteria. CONCLUSIONS: The revised definition of Vogt-Koyanagi-Harada disease, with expanded diagnostic criteria, will facilitate performance of studies involving homogeneous populations of patients, at various stages of disease, that address unanswered questions regarding treatment and disease mechanisms.

PURPOSE: To identify associations between complications of disease and final visual acuity in patients with Vogt-Koyanagi-Harada disease and to identify prognostic factors for disease outcome. METHODS: All patients diagnosed with Vogt-Koyanagi-Harada disease at the Doheny Eye Institute or the Los Angeles County/University of Southern California Medical Center between 1983 and 1997 were reviewed. Data extracted included initial and final visual acuities, age, gender, ethnicity, complications, treatment, duration of disease, and number of recurrences. RESULTS: One hundred one patients with Vogt-Koyanagi-Harada disease were identified, 68 (67%) of which were female. Mean age was 34 ± 14 years (range, 8 to 75 years). Asians presented at a significantly older age than all other groups. One hundred three eyes (51%) developed at least one complication, including cataract in 84 eyes (42%), glaucoma in 54 eyes (27%), choroidal neovascular membranes in 22 eyes (11%), and subretinal fibrosis in 13 eyes (6%). Patients who developed at least one complication had a significantly longer median duration of disease and number of recurrent episodes of inflammation ( P = .0001 for each) than did those patients who developed no complications. Statistically significant associations existed between poor final visual acuity and greater numbers of complications ( P = .001), greater age at onset ( P = .03), a longer median duration of disease ( P = .03), and greater number of recurrent episodes of inflammation ( P = .0004). Eyes possessing a better visual acuity at presentation were more likely to have a better visual acuity at final follow-up ( P = .001). CONCLUSIONS: Factors associated with a worse final acuity included increasing numbers of complications, greater age at onset, and worse acuity at presentation.

Purpose To report a rare case of rhabdomyomatous mesenchymal hamartoma and to compare its features with those cases previously reported. Design Interventional case report and literature review. Intervention Complete ophthalmologic and systemic examinations followed by excisional biopsy and histopathologic examination. Main outcome measures Clinical examination features and histopathologic findings. Results A 6-month-old Latino male presented with a congenital, elevated, smooth, flesh-colored right lower eyelid lesion. An ipsilateral right limbal dermoid and an upper eyelid coloboma were also present. Excisional biopsy of the eyelid lesion revealed randomly oriented mature striated muscle tissue with associated adipose tissue, blood vessels, pilosebaceous units, and peripheral nerves, findings consistent with rhabdomyomatous mesenchymal hamartoma. Of the 24 reported cases (including the current case), eight had associated congenital anomalies. Conclusions Although rhabdomyomatous mesenchymal hamartomas are rare and benign, they may be associated with other congenital anomalies and anomaly syndromes. As a result, we recommend systemic evaluation of patients diagnosed with this entity.

Purpose To describe and clinically characterize a syndrome of self-inflicted scleritis. Study design Case reports and literature review. Methods Two patients had persistent scleritis at presentation. Both did not respond to prescribed therapy, including systemic corticosteroids and immunosuppression. The first had unexplained, diffuse anterior scleritis and persistent linear keratoconjunctival abrasions after a work-related injury. Several objective indicators pointed to concealed noncompliance with medications. The second patient was a medical assistant with diffuse, unilateral anterior scleritis and unexplained visual loss. Systemic work-up was negative. She had pharmacologic mydriasis and keratoconjunctival abrasions at presentation. Results Systemic therapy was stopped in both patients. The first patient, who was in the process of requesting permanent disability status, showed persistent inflammation on each follow-up visit. The second patient improved with no further therapy after she was confronted with objective indicators of a self-inflicted condition. Conclusions Although the presentation of self-inflicted scleritis can be similar to that of idiopathic or autoimmune anterior scleritis, the former may show additional findings of traumatic conjunctival and corneal abrasions. Indicators of self-inflicted etiology, of which malingering is one such entity, include evidence of concealed noncompliance with prescribed treatments and lack of response to potent antiinflammatory and immunosuppressive agents. Correct diagnosis including early psychiatric evaluation in all such cases, may help prevent unnecessary treatment and unjustified work-related compensation.

Sympathetic ophthalmia (SO) is a well-known but rare autoimmune disease in which the sympathizing eye suffers granulomatous panuveitis after trauma to the fellow eye. An unusual case of SO occurring 32 years after trauma to the fellow eye, and 1 year after unsuccessful vitrectomy/scleral buckle repair of an acute retinal detachment in the inciting eye was presented. An optical coherence tomography imagery of Dalen–Fuchs nodules, not previously reported, and rare angiographic imaging of SO in its acute phase was demonstrated.

Objective To evaluate whether an intact respiratory burst exists within the orbit of diabetics with rhinocerebral mucormycosis. Methods Immunohistochemical detection of nitrotyrosine in the orbital tissue of diabetics requiring exenteration due to rhinocerebral mucormycosis. Nitrotyrosine is the stable product of the nitration of tyrosine residues by peroxynitrite. Peroxynitrite is a potent oxidant produced by the combination of superoxide and nitric oxide during the respiratory burst. Results Four specimens were analyzed. All showed focal areas of specific staining against nitrotyrosine of the walls and internal structures of fungal organisms. Conclusions An intact respiratory burst is present in the orbit of diabetics during infection with rhinocerebral mucormycosis. Possible mechanisms of peroxynitrite's microbicidal effects and reasons for a deficiency in diabetics are discussed.

Previous studies of cytomegalovirus (CMV) retinitis have failed to definitively explain the exact mechanism by which CMV gains access to and initiates infection in the retina. Proposed theories have included leakage of the virus through vessels with altered permeability, with subsequent infection of surrounding glial cells. In an attempt to shed further light on this subject, a histopathologic examination of 30 autopsy eyes from patients with known systemic CMV disease was carried out using light microscopy, immunohistochemical and immunofluorescent techniques, and in-situ hybridization. Dual-staining methods were used to identify the exact cell type showing the presence of CMV antigens, namely vascular endothelial cells, glial cells, neuronal cells, and/or leukocytes. In those eyes with CMV retinitis, the sites of full-thickness retinal necrosis revealed viral presence mostly within Müller cells and perivascular glial cells, with focal areas of positive staining within retinal pigment epithelial cells (RPE) and neuronal cells. The retinal capillaries were devoid of endothelial cells in these areas. Adjacent to regions of full-thickness necrosis, some vessels showed the presence of a viral antigen within the endothelial cells. These findings suggest that retinal vascular endothelial cells can be infected with CMV. It can further be hypothesized that infection of vascular endothelial cells leads to infection of the surrounding glial and neuronal cells, with eventual spread to the RPE. Endothelial cells might not be present in areas of full-thickness necrosis due to mechanical forces from adjacent blood flow resulting in the sloughing of these cells.

We report two pediatric female patients with systemic lupus erythematosus (SLE) who presented with decreased vision. Both patients were found to have retinal vasculitis and occlusive disease. The first patient also presented with vitreous hemorrhage and later non-arteritic ischemic optic neuropathy. She was treated with panretinal photocoagulation and steroid therapy and later in her disease course was treated with rituximab and cyclophosphamide. Her vision remained decreased. The second patient was treated with rituximab and monthly cyclophosphamide infusions early in her disease course, and her vision improved dramatically. The difference in the presentations and outcomes of these two pediatric patients with SLE highlights the spectrum of severity of SLE retinopathy. We suggest that early recognition of disease and early intervention with B-cell depletion therapy in addition to a traditional cytotoxic agent should be considered in pediatric patients with SLE and occlusive retinopathy.

Over the 50 years, penetrating keratoplasty (PKP) has progressed from a rare procedure with marginal success to one of the most common and most successful tissue transplants. We review the changing indications for PKP between 1994 and 1998. In decreasing order, the six most common indications were: pseudophakic corneal edema, regraft, unspecified scar, unspecified ulcer, keratoconus, and Fuchs endothelial dystrophy.

Purpose Lipofuscin contained in the retinal pigment epithelium (RPE) is the main source of fundus autofluorescence (FAF), the target of an imaging method useful for estimating the progression of geographic atrophy (GA) in clinical trials. To establish a cellular basis for hyperfluorescent GA border zones, histologic autofluorescence (HAF) was measured at defined stages of RPE pathologic progression. Design Experimental study. Participants and Controls Ten GA donor eyes (mean age ± standard deviation, 87.1±4.0 years) and 3 age-matched control eyes (mean age ± standard deviation, 84.0±7.2 years) without GA. Methods The 10–micrometer-thick sections were divided into zones of RPE morphologic features according to an 8-point scale. Any HAF excited by 488 nm light was imaged by laser confocal microscopy. The HAF intensity summed along vertical lines perpendicular to Bruch's membrane at 0.2-μm intervals served as a surrogate for FAF. Intensity profiles in 151 zones were normalized to grade 0 at a standard reference location in each eye. Cross-sectional area, mean, and sum autofluorescence for individual RPE cells were measured (cellular autofluorescence [CAF]). Main Outcome Measures Statistically significant differences in intensity and localization of HAF and CAF at defined stages of RPE morphologic progression for GA and control eyes. Results The RPE morphologic features were most abnormal (cell rounding, sloughing, and layering; grade 2) and HAF intensity profiles were highest and most variable immediately adjacent to atrophic areas. Peaks in HAF intensity frequently were associated with vertically superimposed cells. The HAF value that optimally separated reactive RPE was 0.66 standard deviations more than the mean for uninvolved RPE and was associated with a sensitivity of 75.8% and a specificity of 76.3%. When variable cell area was accounted for, neither mean nor sum CAF differed significantly among the RPE pathologic grades. Conclusions Areas with advanced RPE alterations are most likely to exhibit clinically recognizable patterns of elevated FAF around GA, but may not predict cells about to die, because of vertically superimposed cells and cellular fragments. These data do not support a role for lipofuscin-related cell death and call into question the rationale of treatments targeting lipofuscin. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Objective To report the occurrence of rifabutin-associated hypopyon uveitis in human immunodeficiency virus (HIV)–negative immunocompetent individuals. Design Retrospective case series. Participants Three HIV-negative subjects on rifabutin and clarithromycin for Mycobacterium avium complex infections with hypopyon uveitis are described. One subject was iatrogenically immunosuppressed because of a prior lung transplant. Two subjects had no known immunosuppressive conditions. Intervention Topical and regional steroid therapy. Discontinuation of rifabutin was required in two subjects. Main outcome measures Visual acuity, resolution of hypopyon, anterior uveitis, and vitreitis. Results All subjects had resolution of hypopyon after therapy, two within 24 hours of beginning topical steroids. Vitreitis resolved with the discontinuation of rifabutin in two subjects. Chronic low-grade anterior uveitis and vitreitis were observed in the remaining subject, whose rifabutin dose was lowered but not discontinued because of active Mycobacterium avium complex osteomyelitis. Conclusions Rifabutin-associated uveitis is well described in HIV-positive individuals, but it has been reported only once in an HIV-negative individual. We report two cases of hypopyon uveitis in immunocompetent individuals and one case in an immunosuppressed HIV-negative individual. All three subjects were receiving concurrent rifabutin and clarithromycin. Awareness that this entity can occur in HIV negative and nonimmunosuppressed individuals and that it can mimic infectious endophthalmitis may spare the subject from an invasive workup of systemic infection.

Objective To describe the characteristics and systemic disease associations of episcleritis in childhood. Design Retrospective, observational case series. Participants Twelve children diagnosed with episcleritis between July 1981 and June 1998. Methods/Testing Complete eye and systemic evaluations. Main outcome measures Characteristics of episcleritis and presence and nature of concurrent systemic disease. Results The 12 children (10 boys and 2 girls) ranged in age from 13 months to 16 years. Five children had bilateral simple episcleritis, one had bilateral nodular episcleritis, and six had unilateral simple episcleritis. The eye examination was otherwise normal and recovery was uneventful in all cases. Six of the nine children older than 5 years of age had one of the following rheumatologic diseases: systemic lupus erythematosus, juvenile rheumatoid arthritis, spondyloarthropathy, inflammatory bowel disease, rheumatic fever, or polyarteritis nodosa. All three children younger than 5 years of age had simple episcleritis, an antecedent viral illness, and presented within 2 months of each other. Conclusions Episcleritis is a rare occurrence in childhood, especially in children younger than 5 years of age. In older children, it is frequently associated with rheumatologic disease.

Purpose To report seven cases of uveitis occurring in patients with autoimmune hepatitis (AIH), raising the possibility that uveitis may be an extrahepatic feature of AIH. Design Multicenter, retrospective, observational case series of patients with AIH and uveitis. Methods One index case was identified at Oregon Health & Science University. Further cases were identified by a web-based survey of members of the American Uveitis Society, the International Uveitis Study Group, the Proctor Foundation mailing list server, and the First SUN International Workshop. Respondents were asked to provide clinical information about uveitis phenotype, AIH features, and treatment. Results Clinical information was obtained for seven individuals (four females and three males; age range, seven to 67 years) who suffered from AIH and uveitis. Average duration of follow-up was 5.5 years. All patients had chronic, persistent bilateral uveitis that was anterior (n = 3), intermediate (n = 1), or pan (n = 3) in location. Every patient had complications arising from his or her uveitis, including cataract (n = 5), glaucoma (n = 3), cystoid macular edema (n = 3), and posterior synechiae (n = 3). Final visual acuities ranged from 20/16 to hand movements. To treat the uveitis and/or AIH, the majority of patients required oral prednisone and all seven patients were treated with systemic immunosuppression. Conclusion Despite the small size of this study, our findings suggest an association between AIH and uveitis. The uveitis is chronic, bilateral, and associated with sight-threatening complications, necessitating systemic immunosuppression in some individuals.

Attachment by ticks to ocular surfaces is uncommon, but has been reported. The objective of this article is to describe a case of conjunctival tick attachment and a method for removal by conjunctival excision. A 39-year-old man presented to the Emergency Department with a complaint of foreign-body sensation in his right eye. He was found to have a live tick embedded in his conjunctiva. The tick was removed en bloc with surrounding conjunctiva by an ophthalmologist. The arthropod was identified as the larval stage of the Lone Star tick (Amblyomma americanum). The patient did not experience any systemic illnesses or adverse sequelae. Attachment of ticks to the conjunctiva is unlikely to result in disease transmission when the larval stage is involved. However, removal by excision of a surrounding block of conjunctiva is recommended to ensure complete removal of all tick body parts.

Purpose To describe the clinical characteristics and course of optic disk edema (ODE) associated with isolated sudden-onset anterior uveitis. Design Interventional, noncomparative retrospective case series. Methods Review of patients with sudden-onset anterior uveitis and concomitant ODE seen in an academic uveitis referral center or a general ophthalmology clinic between August 2001 and November 2002. Results A total of eleven eyes of seven patients were included. Optic nerve function was intact in all. Cranial magnetic resonance imaging was normal in four of five and revealed an abnormality not felt to be responsible for the ODE in one. Resolution of anterior uveitis occurred over a mean of 36 days while ODE resolution lagged by a mean of 20 days. Conclusion Resolution of ODE trailed that of the anterior uveitis by up to 6 weeks. No abnormalities responsible for ODE were found on cranial imaging.

Purpose To describe the histopathology of the cornea in 3 cases of corneal melting associated with diclofenac therapy after refractive surgery procedures. Setting Clinic and pathology laboratory. Methods Three cases of corneal melting associated with diclofenac therapy (2 after laser in situ keratomileusis [LASIK] and 1 after mini-radial keratectomy enhancement of a LASIK undercorrection) were studied using patient and referring physician interviews, chart reviews, and histopathologic examination of the corneal tissue. Results In all 3 cases, the flaps were dislocated and the stromal corneal bed was exposed. Diclofenac, generic or brand name, was used in all cases; in 1 case, both generic and brand name were used. Dosing and duration varied, but in all 3 cases diclofenac was used at least 4 times a day for at least 3 days after LASIK. Topical steroids were also prescribed, but 1 patient did not use them. Preoperative medical conditions were present in 2 cases. Histologic analysis showed evidence of an inflammatory response in advanced cases and keratolysis and lack of inflammatory cells in the flaps that were amputated early. Conclusions The use of generic or brand-name diclofenac with or without adjunctive topical steroids after LASIK can be associated with corneal melting when the LASIK flap is dislodged and the corneal stromal bed exposed. Caution is recommended with diclofenac use after LASIK in such cases.

Purpose To devise methods for unequivocal identification of activated retinal microglia in experimental autoimmune uveoretinitis (EAU) and to investigate their role in the development of EAU. Methods A group of Lewis rats underwent optic nerve axotomy with the application of N-4-(4-didecylaminostyryl)-N methylpyridinium iodide (4Di-10ASP) at the axotomy site. On days 3, 14, and 38 after axotomy, the rats were killed, the eyes were enucleated, and the retinas were stained for OX42. Another group of such axotomized rats were immunized with S-antigen peptide and were killed on days 7 through 12 after the injection with peptide. The enucleated eyes were stained for OX42 and examined by confocal microscope. After axotomy, bone marrow (Y-->X) chimeric rats were injected with S-antigen peptide and were killed on days 10 and 12 after injection. The retinas were evaluated by PCR with Y-specific primers. Finally, a group of axotomized rats was injected with the S-antigen peptide and killed on days 6, 8, 9, and 10 after injection. Their enucleated eyes were examined for microglial expression of TNFalpha and for generation of peroxynitrite. Results In the axotomized, non-EAU eyes, 4Di-10ASP-labeled ganglion cells were detectable on days 3 and 14, and 4Di-10ASP-containing OX42-positive cells (microglia) were found in the nerve fiber and other inner retinal layers on days 14 and 38. The S-antigen peptide-injected rats showed migration of the microglia (4Di-10ASP-positive and OX42-positive) to the photoreceptor cell layer on day 9, and these cells increased in number at this site on day 10. No macrophages (OX42-positive and 4Di-10ASP-negative) were present at this early stage of EAU, but such cells appeared in the retina on days 11 and 12. PCR of the chimeric EAU retinas showed an absence of the Y chromosome-amplified product on day 10, but the presence of this product was detected on day 12. The expression of TNFalpha and generation of peroxynitrite were noted in the migrated microglia at the photoreceptor cell layer on days 9 and 10 of EAU. Conclusions In the early phase of EAU, the microglia migrate to the photoreceptor cell layer where they generate TNFalpha and peroxynitrite. Such microglial migration and activation take place before infiltration of the macrophages. These findings indicate a novel pathogenic mechanism of EAU, in which retinal microglia may initiate retinitis with subsequent recruitment of circulation-derived phagocytes, leading to the amplification of uveoretinitis.