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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.

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 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.

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.

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: 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.

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.

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.

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 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.

PURPOSE: To report a case of adenocarcinoma metastatic to the choroid with rupture through the Bruch membrane, thus, simulating a choroidal melanoma. METHODS: Interventional case report. Evaluation in a university-based clinic, including a complete eye examination, fluorescein angiography, and ultrasonography; oncological evaluation; and eventual enucleation with histopathological study, including immunohistochemical stains. RESULTS: A 62-year-old Hispanic female presented with visual loss, right eye, of short duration because of a choroidal mass with retinal detachment. Ultrasonography showed a dome-shaped lesion with an eccentric collar-button projection and medium internal reflectivity, which suggested a choroidal melanoma. Initial systemic evaluation was negative. Severe pain necessitated enucleation, RE, and histopathology of the choroidal mass demonstrated an adenocarcinoma. Further examination revealed a left, upper lobe, nonsmall cell lung carcinoma. CONCLUSION: Metastatic choroidal tumors may present, although rarely, with collar-button configurations.

The diagnosis of Vogt-Koyanagi-Harada syndrome is hampered by its variable manifestations and the lack of unique ancillary and laboratory findings. In this study, the diagnostic criteria established in 1978 by the American Uveitis Society (AUS) are retrospectively analyzed via their application to a population of 71 consecutive patients, using only those features present at the initial evaluation. All patients were previously diagnosed with Vogt-Koyanagi-Harada syndrome based on the clinical features and course of the disease combined with fluorescein angiography with or without ultrasonography in selected cases. Mean age of all patients was 36.7 years +/- 15.1 years. Fifty (70%) were female and 45 (65%) were Hispanic. Patients presenting acutely, subacutely, and in the chronic stages met the AUS criteria for Vogt-Koyanagi-Harada syndrome in 56%, 48%, and 58% of cases, respectively. Allowance for variation in features, incomplete cases, and modification of the disease by treatment might increase the sensitivity of the criteria. While diagnostic criteria in general are useful for establishing the likelihood that a patient has a disease, the current AUS criteria for the diagnosis of Vogt-Koyanagi-Harada syndrome do not seem adequate.

Vogt-Koyanagi-Harada (VKH) disease affects primarily persons who are Asian, Latino, Native American, or Asian Indian. Women appear to be affected more commonly than men, and VKH disease may occur at all ages, including childhood. Experimental data continue to support an autoimmune etiology for VKH disease, directed most probably against an antigenic component of the melanocyte, possibly tyrosinase or a tyrosinase-related protein. The clinical diagnosis of VKH disease continues to be based on physical findings. Newer imaging modalities such as magnetic resonance imaging, indocyanine green angiography, and digital image analysis have not added appreciably to our understanding of the condition. First-line therapy consists of high-dose corticosteroids, with use of corticosteroid-sparing agents for resistant or recalcitrant disease. Complications are the main cause of reversible and irreversible vision loss, with subretinal fibrosis and choroidal neovascular membranes having particularly poor prognoses.

A 52-year-old man underwent bilateral laser-assisted in situ keratomileusis. Eight months later, he sustained a penetrating corneal injury to the left eye. A dense white infiltrate, unresponsive to antimicrobial therapy, developed in the corneal stroma. Corneal biopsy and eventual penetrating keratoplasty were performed, and both specimens demonstrated fungal elements with branching, septate hyphae. Culture identified the organism as Acremonium atrogriseum. Histopathologic features of this organism and its differentiation from other, more common fungal organisms are discussed herein.

A 69-year-old woman with no history of malignant disease presented with complaints of ptosis, diplopia, and left upper eyelid fullness. Computed tomography showed soft tissue infiltration of the left superior orbit. Biopsy was performed through an anterior orbitotomy. Histopathology revealed a mucinous adenocarcinoma. Subsequent systemic evaluation included esophagogastroduodenoscopy, which revealed a primary gastric malignancy.

Vogt-Koyanagi-Harada disease (VKH) is a visually disabling bilateral intraocular inflammation usually associated with extraocular manifestations such as meningismus, vitiligo, poliosis, and dysacusis.1–3 The extraocular manifestations typically appear in different phases of the disease and may vary in different ethnic groups.1, 4–6 For example, cutaneous manifestations are typically absent during the acute phase and appear later in the disease course, while the neurologic and auditory manifestations generally precede ocular manifestations. The absence of concurrent extraocular manifestations may have significant implications for both clinical practice and the conduct of clinical studies, as follows. In the area of clinical practice, variation in manifestations and their timing may cause a delay in establishing the correct diagnosis and thus a delay in the initiation of appropriate treatment. This may result in the disease entering the chronic/recurrent phase and in the subsequent development of complications such as glaucoma, cataract, and subretinal neovascularization or fibrosis.1, 7–10 In the area of clinical research, in addition to the issue described for clinical practice, VKH is a relatively uncommon disease and future clinical studies will require international collaboration and pooling of patients of various ethnicities to achieve numbers of subjects sufficient for meaningful conclusions to be drawn. Variations in the presentation of VKH patients can make it difficult to ensure that all subjects enrolled in a clinical study truly have VKH disease. To this end, various diagnostic criteria have been created,4, 11, 12 but developing criteria that are broad enough to encompass the various ways in which VKH may present, while ensuring that non-VKH patients are excluded, is difficult. In addition, none of the published sets of criteria, to our knowledge, has been created based on a sound statistical analysis of the most common and distinguishing manifestations of the disease. As a basis for the development of a statistically and epidemiologically validated set of diagnostic findings, the current multinational study was undertaken to define the clinical features which distinguish VKH from other forms of uveitis.

Editor,—A 60 year old woman presented with intense, bilateral ocular irritation and photophobia. She had a history of rheumatoid arthritis and was under treatment with prednisone, azathioprine, sulindac, plaquenil, and intramuscular injections of gold sodium thiomaleate (50 mg once weekly). She had received a total of 7.4 g of gold over the past 3 years. Examination revealed an extremely photophobic patient with a visual acuity of 20/20 in both eyes. The conjunctivas were mildly injected, with bilateral perilimbal chemosis. The peripheral cornea showed 360° stromal oedema. Mid-stromal vessels were seen entering the oedematous stroma from the limbus (Fig 1(left)). The rest of the examination was unremarkable. The patient was diagnosed with rheumatoid marginal keratitis, and therapy was started with hourly application of topical prednisolone acetate. Over …