Narsing A. Rao

Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report of an international committee on nomenclature.

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.

Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy

Summary Background In previous natural history studies and clinical trials, AIDS-related cytomegalovirus (CMV) retinitis has occurred primarily in patients with absolute CD4 counts of 50 cells/μL or less (0·05×10 9 /L) at the time of diagnosis. Methods We report five patients identified from our clinical practices who were diagnosed with CMV retinitis while their CD4 counts were above 195 cells/μL. We also analysed, based on CD4 counts, 76 AIDS patients with newly diagnosed CMV retinitis whose CD4 lymphocyte enumerations were done in laboratories that maintained certification in a common external quality control programme. Findings 5–24 weeks before retinitis was diagnosed, all five patients had had absolute CD4 lymphocyte counts of less than 85 cells/μL, and 4–7 weeks before diagnosis, all five patients had started taking highly active antiretroviral treatment (HAART) regimens. Only one (4%) of 27 patients enrolled in the trial between July, 1995, and February, 1996, had an absolute CD4 count of more than 50 cells/μL, and none of 27 had an absolute CD4 count of more than 100/μL on entry to the trial. However, from March, 1996 (when indinavir and ritonavir were approved by the FDA for marketing in the USA), to August, 1996, 14 (29%) of 49 patients had CD4 counts of more than 50/μL and seven (14%) of 49 had a CD4 count of more than 100 cells/μL on entry. Interpretation These findings suggest that the early immunological effects of HAART may not provide sufficient protection to prevent CMV retinitis in patients who have very low CD4 counts when therapy is started. Clinicians should note that CMV retinitis may now occur in patients who have CD4 counts of more than 100 cells/μL.

Changing Patterns of Uveitis

We conducted a retrospective analysis of 600 patients with uveitis seen at the Estelle Doheny Eye Center to determine the frequency of occurrence of the various forms of uveitis and to see if the causes of uveitis have changed as compared with previous studies. In 402 cases (67.0%) we established a specific diagnosis based on history, physical findings, and laboratory studies: 167 cases (27.8%) involved primarily the anterior segment, 230 (38.4%) the posterior segment, and 111 (18.4%) occurred as panuveitis. Intermediate uveitis (pars planitis) was the single most frequently diagnosed uveitic entity and accounted for 92 cases (15.4%). We compared our findings with those of previously published studies and found that, as new diseases occur and improved diagnostic techniques become available, the differential diagnosis of uveitis continues to change.

International Criteria for the Diagnosis of Ocular Sarcoidosis: Results of the First International Workshop on Ocular Sarcoidosis (IWOS)

Aim: To report criteria for the diagnosis of intraocular sarcoidosis, taking into account suggestive clinical signs and appropriate laboratory investigations and biopsy results. Design: Concensus workshop of an international committee on nomenclature. Methods: An international group of uveitis specialists from Asia, Africa, Europe, and America met in a concensus conference in Shinagawa, Tokyo on October 28–29, 2006. Based on questionnaires that had been sent out prior to the conference, the participants discussed potential intraocular clinical signs eligible for a diagnosis of ocular sarcoidosis. A refined definition of clinical signs, which received two-thirds majority of votes, was included in the list of signs consistent with ocular sarcoidosis. Laboratory investigations were similarly discussed and those tests reaching a two-thirds majority were retained for the diagnosis of ocular sarcoidosis. Finally diagnostic criteria were proposed based on ocular signs, laboratory investigations, and biopsy results. Results: The concensus conference identified seven signs in the diagnosis of intraocular sarcoidosis: (1) mutton-fat keratic precipitates (KPs)/small granulomatous KPs and/or iris nodules (Koeppe/Busacca), (2) trabecular meshwork (TM) nodules and/or tent-shaped peripheral anterior synechiae (PAS), (3) vitreous opacities displaying snowballs/strings of pearls, (4) multiple chorioretinal peripheral lesions (active and/or atrophic), (5) nodular and/or segmental peri-phlebitis (± candlewax drippings) and/or retinal macroaneurism in an inflamed eye, 6) optic disc nodule(s)/granuloma(s) and/or solitary choroidal nodule, and (7) bilaterality. The laboratory investigations or investigational procedures that were judged to provide value in the diagnosis of ocular sarcoidosis in patients having the above intraocular signs included (1) negative tuberculin skin test in a BCG-vaccinated patient or in a patient having had a positive tuberculin skin test previously, (2) elevated serum angiotensin converting enzyme (ACE) levels and/or elevated serum lysozyme, (3) chest x-ray revealing bilateral hilar lymphadenopathy (BHL), (4) abnormal liver enzyme tests, and (5) chest CT scan in patients with a negative chest x-ray result. Four levels of certainty for the diagnosis of ocular sarcoidosis (diagnostic criteria) were recommended in patients in whom other possible causes of uveitis had been excluded: (1) biopsy-supported diagnosis with a compatible uveitis was labeled as definite ocular sarcoidosis; (2) if biopsy was not done but chest x-ray was positive showing BHL associated with a compatible uveitis, the condition was labeled as presumed ocular sarcoidosis; (3) if biopsy was not done and the chest x-ray did not show BHL but there were 3 of the above intraocular signs and 2 positive laboratory tests, the condition was labeled as probable ocular sarcoidosis; and (4) if lung biopsy was done and the result was negative but at least 4 of the above signs and 2 positive laboratory investigations were present, the condition was labeled as possible ocular sarcoidosis. Conclusion: Various clinical signs, laboratory investigations, and biopsy results provided four diagnostic categories of sarcoid uveitis. The categorization allows prospective multinational clinical trials to be conducted using a standardized nomenclature, which serves as a platform for comparison of visual outcomes with various therapeutic modalities.

Ocular toxoplasmosis in patients with the acquired immunodeficiency syndrome

In seven of eight cases of presumed ocular toxoplasmosis in patients with AIDS, the diagnosis was supported by a reduction or resolution of intraocular inflammation and healing of necrotic retinal lesions after initiation of antiparasitic drug therapy including one or more of the following medications: pyrimethamine, sulfadiazine, clindamycin, tetracycline, or spiramycin. In two cases the diagnosis was confirmed histologically. The cases differed clinically and histopathologically from those in immunocompetent patients. There was no evidence that disease originated in preexisting retinochoroidal scars. Lesions frequently were bilateral and multifocal. Vitreous inflammatory reaction was a common clinical finding, but histopathologic examination demonstrated scant retinal inflammation in areas of necrosis. Ocular toxoplasmosis in these patients with AIDS probably resulted from newly acquired infection or dissemination of organisms from nonocular sites of disease. Infections became clinically inactive with drug therapy in all treated patients, but reactivation and progression of disease occurred when therapy was stopped in two of three patients. Severe retinal necrosis led to retinal tears or detachment in three cases. Ocular lesions were the first manifestation of Toxoplasma gondii infection in four of five patients with evidence of multisystem infection.

Rapidly Progressive Outer Retinal Necrosis in the Acquired Immunodeficiency Syndrome

Two patients, both seropositive for the human immunodeficiency virus, developed rapidly progressive retinal necrosis associated with a systemic herpes zoster infection. The retinitis in these patients was characterized by primary involvement of the outer retina, with sparing of the inner retina and retinal vasculature until late in the disease process; a rapidly progressive course; poor response to intravenous acyclovir; and development of rhegmatogenous retinal detachment. In one of the patients, the retinitis was initially multifocal. Electron microscopy of a retinal biopsy specimen from one of the patients demonstrated virus particles consistent with a herpesvirus, and polymerase chain reaction disclosed herpesvirus in a retinal biopsy specimen of the other patient. This entity may represent a distinct form of acute retinal necrosis that is seen in immunocompromised individuals.

Cytomegalovirus Retinitis and Response to Therapy with Ganciclovir

A 15-month prospective study of 109 patients with the acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) was conducted. Cytomegalovirus (CMV) retinitis developed in 18 of these patients; they were treated with ganciclovir. Five other patients with CMV retinitis who were not part of the prospective study were also treated with ganciclovir. CMV retinitis frequently involved the peripheral retina. All 23 patients treated with ganciclovir showed clinical regression of retinitis, although breakthrough recurrence of CMV retinitis occurred in seven patients (30.4%) while on maintenance therapy with ganciclovir. During treatment, neutropenia (less than 1000 leukocytes/mm3) developed in three patients (13%). Ganciclovir is an effective means of therapy for CMV retinitis, but it must be given chronically to prevent reactivation. Breakthrough recurrences while on maintenance therapy are not uncommon, but can be successfully treated with more aggressive treatment with ganciclovir. In addition, the prognosis for survival of AIDS patients being treated with ganciclovir is improved when compared with that of untreated patients.

Complications and prognostic factors in Vogt-Koyanagi-Harada disease☆

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.

Cataract extraction in uveitis patients

Cataracts are known to develop at an accelerated rate in many forms of uveitis. Until recently, cataract surgery in such eyes was regarded as a hazardous procedure that yielded unpredictable and often discouraging results. Recent evidence from a number of reports suggests that newer surgical techniques and careful medical management allow a significant number of patients with uveitis to undergo cataract extraction successfully. Intraocular lens implantation using in-the-bag posterior chamber lens technique has been successful in selected cases. Careful patient selection, coupled with the use of an appropriate surgical technique, appear to be of major importance. Herein we review the current literature on cataract extraction in uveitis and provide guidelines for patient and technique selection based on the type of inflammation present. The management of common surgical problems and complications is discussed, as is the role of the intraocular lens. Specific surgical techniques useful in the management of eyes with cataract and uveitis are discussed.

Prevalence, Pathophysiology, and Treatment of Rhegmatogenous Retinal Detachment in Treated Cytomegalovirus Retinitis

Seventeen patients with the acquired immune deficiency syndrome and cytomegalovirus retinitis were treated with the antiviral drug ganciclovir (9-[1,3-dihydroxy-2-propoxy-methyl]-guanine, DHPG). Eight eyes of five patients developed rhegmatogenous retinal detachment after initiation of treatment. Multiple breaks in areas of peripheral, healed, atrophic retina accounted for the detachments. All seven eyes that underwent surgery had extensive retinal detachments that were reattached with vitrectomy and silicone oil. Retinotomy and retinal tacks were necessary in two cases that were complicated by severe proliferative vitreoretinopathy. In the fellow eye of one patient, laser treatment was used prophylactically to wall off a peripheral patch of healed retinitis. Endoretinal biopsies and culture were taken in five eyes; evidence of persistent cytomegalovirus was seen in two cases despite concurrent and clinically effective antiviral therapy.