Visual acuity outcomes in cytomegalovirus retinitis: early versus late diagnosis.

AIMS: To determine if early dilated fundus examination for cytomegalovirus (CMV) retinitis leads to better visual outcomes in areas with limited HIV care, where patients may have long-standing retinitis before they are diagnosed with HIV. METHODS: Twenty-four eyes of 17 patients with CMV retinitis who were seen at an urban HIV clinic in Chiang Mai, Thailand, were included in this retrospective cohort study. Participants were divided into two groups based on the amount of time from the first documented CD4 count below 100 cells/mm3 to the first eye examination for CMV retinitis. Average visual acuity in each group was calculated at the time CMV retinitis was first detected, and then at 3, 6 and 12 months after diagnosis. RESULTS: The group of patients who received an eye examination within approximately 4 months of the initial low CD4 count measurement had better baseline visual acuity (median 20/30,IQR 20/20 to 20/60) compared with patients who presented later (median 20/80, 20/60 to hand motion); p=0.03). Visual acuity did not change significantly during the 12-month study period in either the early group (p=0.69) or late group (p=0.17). CONCLUSION: In this study, patients who were examined sooner after a low CD4 count had better vision than patients who were examined later. Routine early screening of patients with CD4 counts under below 100 cells/mm3 may detect earlier disease and prevent vision loss.

Fundus findings in a series of patients with extrapulmonary tuberculosis in Thailand.

AIM: The aim of this study was to determine the frequency of fundus abnormalities among patients who are undergoing or have recently completed treatment for extrapulmonary tuberculosis (eTB). METHODS: This is a prospective cross-sectional study conducted in a TB clinic of a tertiary hospital in northern Thailand. All patients who had eTB between January 2014 and August 2015 were invited by telephone to return to the clinic for fundus photography. Three uveitis specialists reviewed all photographs to identify posterior segment lesions that were consistent with ocular TB. RESULTS: A total of 265 patients were diagnosed with eTB during the specified period, of which 118 (44.5%) were reached by telephone and 60 (50.8%) participated in the study. A total of 7 eyes from six patients (10.0% of participants, 95% CI 2.2% to 17.8%) had lesions consistent with ocular TB. The group with possible ocular TB lesions was on average 16.8 years older than those without ocular lesions (p=0.01), but the two groups were otherwise not significantly different. CONCLUSION: Ocular lesions consistent with TB were not rare in a group of patients who were undergoing or had recently completed treatment for eTB. Fundus examination may provide diagnostic information that could influence a clinician's beliefs when diagnosing eTB. Given the low costs and immediate results of eye examination, this diagnostic test should be considered in patients suspected for eTB, especially when other tests are negative.

Diagnostic Utility of Ocular Symptoms and Vision for Cytomegalovirus Retinitis.

PURPOSE: Cytomegalovirus (CMV) retinitis remains a leading cause of blindness in countries with a high burden of AIDS. Although dilated fundus examinations are recommended for those with CD4 counts below 100 cells/µL, in practice only those with poor vision and/or symptoms are routinely referred for screening. Therefore, the predictive value of this common practice should be assessed. METHODS: This is a prospective cross-sectional study. Patients with known HIV and a CD4 count of less than 100 cells/µL attending an HIV clinic in Chiang Mai, Thailand completed a standardized questionnaire about visual symptoms and underwent visual acuity testing and dilated fundus examination. Participants without CMV retinitis were invited for repeated examinations every 3 months until their CD4 count exceeded 100 cells/µL. Patient-level statistical analyses were conducted to calculate diagnostic test characteristics, with bootstrapping to account for correlated data. RESULTS: Of 103 study participants, 16 had CMV retinitis diagnosed at some point during the study. Participants with CMV retinitis were more likely to complain of visual symptoms compared to those without CMV retinitis (p = 0.01), including scotoma (p = 0.0002), itchy or watery eyes (p < 0.0001), and eye pain (p = 0.003); they were also more likely to have visual acuity worse than Counting Fingers (p = 0.0003). However, the absence of eye symptoms and the absence of poor vision did not strongly affect the probability that a patient did not have disease (negative likelihood ratio 0.56 and 0.76, respectively). CONCLUSIONS: Ocular symptoms and poor visual acuity were poor diagnostic indicators for the presence of CMV retinitis. Systematic screening of HIV patients with CD4 counts below 100 cells/µl should be carried out to detect disease at an early stage, when blindness can still be prevented.

Risk factors for CMV retinitis among individuals with HIV and low CD4 count in northern Thailand: importance of access to healthcare.

AIM: To determine if poor access to healthcare is associated with increased cytomegalovirus (CMV) retinitis risk among patients with HIV with CD4 counts of <100 cells/µL screened in a resource-limited setting. METHODS: This is a prospective cross-sectional study. Patients with known HIV and a CD4 count of <100 cells/µL attending an HIV clinic in Chiang Mai, Thailand, completed a standardised questionnaire and underwent dilated fundus examination. Participants without CMV retinitis were invited for repeated examinations every 3 months until their CD4 count exceeded 100 cells/µL. The relationship between various potential risk factors and CMV retinitis was assessed with logistic regression. RESULTS: 103 study participants were enrolled. At enrolment, the mean age was 37.5 (95% CI 35.7 to 39.2) years, 61.2% (95% CI 51.6% to 70.7%) were male and the mean CD4 count was 29.5 (95% CI 25.9 to 33.1) cells/µL. 21 eyes from 16 (15.5%) participants were diagnosed with CMV retinitis. In multivariate analyses, CMV retinitis was significantly associated with lower CD4 count (OR 1.42 per 10-cell decrement, 95%CI 1.05 to 1.93), longer travel time to clinic (OR 3.85 for those with >30-min travel time, 95% CI 1.08 to 13.8) and lower income (OR 1.22 per US$50 less income, 95% CI 1.02 to 1.47). CONCLUSIONS: CD4 count, low income and longer travel time to clinic were significant risk factors for CMV retinitis among patients with HIV in a resource-limited setting. These results suggest that reducing blindness from CMV retinitis should focus on increasing accessibility of screening examinations to poor and hard-to-reach patients.

Retinal detachment associated with AIDS-related cytomegalovirus retinitis: risk factors in a resource-limited setting.

PURPOSE: To determine risk factors predictive of retinal detachment in patients with cytomegalovirus (CMV) retinitis in a setting with limited access to ophthalmic care. DESIGN: Case-control study. METHODS: Sixty-four patients with CMV retinitis and retinal detachment were identified from the Ocular Infectious Diseases and Retina Clinics at Chiang Mai University. Three control patients with CMV retinitis but no retinal detachment were selected for each case, matched by calendar date. The medical records of each patient were reviewed, with patient-level and eye-level features recorded for the clinic visit used to match cases and controls, and also for the initial clinic visit at which CMV retinitis was diagnosed. Risk factors for retinal detachment were assessed separately for each of these time points using multivariate conditional logistic regression models that included 1 eye from each patient. RESULTS: Patients with a retinal detachment were more likely than controls to have low visual acuity (odds ratio [OR], 1.24 per line of worse vision on the logMAR scale; 95% confidence interval [CI], 1.16-1.33) and bilateral disease (OR, 2.12; 95% CI, 0.92-4.90). Features present at the time of the initial diagnosis of CMV retinitis that predicted subsequent retinal detachment included bilateral disease (OR, 2.68; 95% CI, 1.18-6.08) and lesion size (OR, 2.64 per 10% increase in lesion size; 95% CI, 1.41-4.94). CONCLUSION: Bilateral CMV retinitis and larger lesion sizes, each of which is a marker of advanced disease, were associated with subsequent retinal detachment. Earlier detection and treatment may reduce the likelihood that patients with CMV retinitis develop a retinal detachment.

Telemedicine screening for cytomegalovirus retinitis at the point of care for human immunodeficiency virus infection.

IMPORTANCE: Cytomegalovirus (CMV) retinitis is a leading cause of blindness in many developing countries, likely the result of inadequate screening. Telemedicine screening for CMV retinitis instituted at the point of care for human immunodeficiency virus (HIV) infection may allow for earlier detection. OBJECTIVES: To determine the diagnostic accuracy of retinal photography in detecting CMV retinitis at the point of HIV care and to characterize the clinical manifestations of CMV retinitis detected through the screening program. DESIGN, SETTING, AND PARTICIPANTS: We enrolled 103 participants from a population of 258 patients with HIV and a CD4 level of less than 100/µL treated at an HIV clinic in Thailand from June 2010 through June 2012. We captured mosaic fundus photographs through a dilated pupil using a digital fundus camera. An experienced on-site ophthalmologist masked to the results of the fundus images subsequently examined each eye with indirect ophthalmoscopy and recorded the clinical findings on a standardized form. Three remote graders evaluated each image for CMV retinitis. INTERVENTION: Fundus photography and indirect ophthalmoscopy. MAIN OUTCOMES AND MEASURES: Sensitivity and specificity of telemedicine relative to indirect ophthalmoscopy for diagnosis of CMV retinitis and clinical features of CMV retinitis lesions. RESULTS: Sixteen patients (15.5%) were diagnosed as having CMV retinitis, of whom 5 (31%) had bilateral disease. Of the 21 eyes (10.2%) with CMV retinitis, 7 (33%) had visual symptoms. Retinitis lesions occupied less than 10% of the total retinal surface area in 13 of 21 eyes (62%) and did not involve the posterior pole (ie, zone 1) in 15 of 21 eyes (71%). Mean logMAR visual acuity in affected eyes was 0.41 (95% CI, 0.11-0.71; Snellen equivalent, 20/50 [95% CI, 20/25-20/100]). The mean sensitivity for the 3 remote graders in detecting CMV retinitis on fundus photography was 30.2% (95% CI, 10.5%-52.4%), and mean specificity was 99.1% (95% CI, 97.8%-100.0%). The CMV retinitis lesions missed by the remote graders (false-negative findings) were more likely to be small (P = .001) and located in the peripheral retina (P = .04). CONCLUSIONS AND RELEVANCE: Patients undergoing screening at a clinic for HIV treatment had less extensive retinitis than patients in recent reports from an ophthalmology clinic. Retinal photography with the camera used in this study was not highly sensitive in detecting CMV retinitis but may identify disease with an immediate threat to vision. Improved accuracy will require a camera that can more easily image the peripheral retina.

Telemedicine diagnosis of cytomegalovirus retinitis by nonophthalmologists.

IMPORTANCE: Cytomegalovirus (CMV) retinitis continues to be a leading cause of blindness in many developing countries. Telemedicine holds the potential to increase the number of people screened for CMV retinitis, but it is unclear whether nonophthalmologists could be responsible for interpreting fundus photographs captured in a telemedicine program. OBJECTIVE: To determine the accuracy of nonophthalmologist photographic graders in diagnosing CMV retinitis from digital fundus photographs. DESIGN, SETTING, AND PARTICIPANTS: Fifteen nonexpert graders each evaluated 182 mosaic retinal images taken from the eyes of patients with AIDS who were evaluated at the Ocular Infectious Diseases Clinic at Chiang Mai University in Chiang Mai, Thailand. MAIN OUTCOMES AND MEASURES: Graders diagnosed each image as CMV retinitis present, CMV retinitis absent, or unknown. The results from each grader were compared with those of an indirect ophthalmoscopic examination from an experienced on-site ophthalmologist as well as with the consensus grade given by a panel of CMV retinitis experts. RESULTS: Relative to the on-site ophthalmologist, the sensitivity of remote CMV retinitis diagnosis by nonexpert graders ranged from 64.0% to 95.5% (mean, 84.1%; 95% CI, 78.6%-89.6%)), and the specificity ranged from 65.6% to 92.5% (mean, 82.3%; 95% CI, 76.6%-88.0%)). Agreement between nonexpert and expert graders was high: the mean sensitivity and specificity values of nonexpert diagnosis using expert consensus as the reference standard were 93.2% (95% CI, 90.6%-95.8%) and 88.4% (95% CI, 85.4%-91.1%), respectively. Mean intrarater reliability also was high (mean Cohen κ, 0.83; 95% CI, 0.78-0.87). CONCLUSIONS AND RELEVANCE: The sensitivity and specificity of remote diagnosis of CMV retinitis by nonexpert graders was variable, although several nonexperts achieved a level of accuracy comparable to that of CMV retinitis experts. More intensive training and periodic evaluations would be required if nonexperts are to be used in clinical practice.

Access to ophthalmologic care in Thailand: a regional analysis.

PURPOSE: The World Health Organization (WHO) recommends that Southeast Asian countries have ≥ 1 ophthalmologist per 100,000 persons, equally distributed in urban and rural areas. However, regional patterns of eye care have been poorly characterized. This study investigates the distribution of ophthalmologists in Thailand and provides regional estimates of access to ophthalmologists. METHODS: We geocoded the work address of ophthalmologists listed in the 2008 directory of the Royal College of Ophthalmologists of Thailand. We determined the number of ophthalmologists per 100,000 persons at the national, provincial, and district levels using data from the 2000 Thai Population Census, and assessed demographic factors associated with meeting the WHO recommendation of ≥ 1 ophthalmologist per 100,000 persons. RESULTS: In 2008, Thailand had 1.52 ophthalmologists per 100,000 persons; however, only 20 of 76 provinces (26%) and 134 of 926 districts (14%) met the WHO recommendation of ≥ 1 ophthalmologist per 100,000 persons. District factors associated with not meeting the WHO recommendation included a high proportion of children, a high proportion of elderly, and a high proportion of rural residents. CONCLUSION: Thailand meets the WHO's goal for access to ophthalmologic care, but the distribution of ophthalmologists is uneven, with less access to ophthalmologic care in rural areas.

Intravitreal bevacizumab at the end of diabetic vitrectomy for prevention of postoperative vitreous hemorrhage: a comparative study.

OBJECTIVE: To study the role of intravitreal injection of bevacizumab (Avastin) at the end of vitrectomy for prevention of postoperative vitreous hemorrhage in diabetic eye disease. MATERIAL AND METHOD: The authors conducted a retrospective, comparative, nonrandomized study comparing patients with diabetic eye disease who received a 1.25 mg bevacizumab injection at the end of vitrectomy to a group with diabetic eye disease who underwent vitrectomy but did not receive this injection. For statistical analysis, each patient was assigned to one of four groups according to the hemostatic modalities used (group 1, none; group 2, only long acting gas; group 3, only intraoperative intravitreal bevacizumab; group 4, both long acting gas and intraoperative intravitreal bevacizumab). The primary outcome measure was the incidence of early and late postoperative vitreous hemorrhage (POVH). The secondary outcome measure was visual acuity (VA) at 1 and 6 months. RESULTS: The present study included 87 eyes from 78 patients. The 87 eyes were categorized in the four groups described above. The incidence of early postoperative VH was lowest in group 3 (50%), followed by group 1 and group 4 (130%) and group 2 (16%) (p = 0.49). No eyes in group 1 or group 4 had late postoperative VH. Group 3 had the lowest incidence of VA below 20/200 (11%) in the first postoperative month, followed by group 1 (22%), group 4 (33%) and group 2 (50%) (p = 0.44). Group 3 also had the best visual recovery (VA above 20/50) with 38% at the end of six months compared with 13% in group 1, 7% in group 4 and no eyes in group 2 (p = 0.03). CONCLUSION: Patients with intravitreal injection of 1.25 mg bevacizumab at the end of diabetic vitrectomy had the lowest incidence of early postoperative vitreous hemorrhage with no statistical significance. However they had significantly the best visual recovery at the end of six months.

Clinical features of newly diagnosed cytomegalovirus retinitis in northern Thailand.

PURPOSE: To characterize the clinical manifestations of cytomegalovirus (CMV) retinitis in northern Thailand. DESIGN: Prospective, observational, cross-sectional study. METHODS: We recorded characteristics of 52 consecutive patients newly diagnosed with CMV retinitis at a tertiary university-based medical center in northern Thailand. Indirect ophthalmoscopy by experienced ophthalmologists was supplemented with fundus photography to determine the proportion of eyes with various clinical features of CMV retinitis. RESULTS: Of the 52 patients with CMV retinitis, 55.8% were female. All were HIV-positive. The vast majority (90.4%) had started antiretroviral therapy. CMV retinitis was bilateral in 46.2% of patients. Bilateral visual acuity worse than 20/60 was observed in 23.1% of patients. Of 76 eyes with CMV retinitis, 61.8% had zone I disease and 21.6% had lesions involving the fovea. Lesions larger than 25% of the retinal area were observed in 57.5% of affected eyes. CMV retinitis lesions commonly had marked or severe border opacity (47.4% of eyes). Vitreous haze often was present (46.1% of eyes). Visual impairment was more common in eyes with larger retinitis lesions. Retinitis lesion size, used as a proxy for duration of disease, was associated with fulminant appearance (odds ratio, 1.24; 95% confidence interval, 1.01 to 1.51) and marked or severe border opacity (odds ratio, 1.36; 95% confidence interval, 1.11 to 1.67). Based on lesion size, retinitis preceded antiretroviral treatment in each patient. CONCLUSIONS: Patients seeking treatment at a tertiary medical center in northern Thailand had advanced CMV retinitis, possibly because of delayed diagnosis. Earlier screening and treatment of CMV retinitis may limit progression of disease and may prevent visual impairment in this population.

Comparison of autophotomontage software programs in eyes with CMV retinitis.

PURPOSE: Automated mosaic software programs are used to stitch together overlapping retinal fundus photographs. The performance of these programs in eyes with retinal diseases has not been independently evaluated. This study compares the quality of the mosaic products of three autophotomontage software programs, using digital fundus photographs of eyes with cytomegalovirus (CMV) retinitis. METHODS: Photographs of 99 eyes with CMV retinitis of 94 patients with HIV were taken at Maharaj Nakorn Chiang Mai Hospital in Chiang Mai, Thailand. Automated mosaic images were created for each of the 99 eyes by three different commercially available programs: IMAGEnet (Topcon, Oakland, NJ), i2k Retina (DualAlign LLC, Clifton Park, NY), and AutoMontage (OIS, Sacramento, CA). Three masked graders ranked each set of mosaics for each eye. The graders also assessed the overall image quality and documented mosaic artifacts in each image. RESULTS: i2k Retina was ranked as the best program (70%-88%) more often than AutoMontage (10%-33%, P < 0.001) or IMAGEnet (0%-4%, P < 0.001) for creating automontages from digital fundus photographs of eyes with CMV retinitis. Acceptable quality mosaic images were reported most commonly for i2k Retina (93%-94%) and AutoMontage (91%-95%), followed by IMAGEnet (27%-56%, P < 0.001). IMAGEnet had a significantly higher percentage of mosaic errors than did either i2k Retina or AutoMontage (P < 0.001). CONCLUSIONS: In eyes with CMV retinitis, both the i2k Retina and AutoMontage software packages appear to create higher quality mosaics than does IMAGEnet. Automated retinal mosaic imaging may be valuable in diagnosing CMV retinitis and observing disease progression.

Accuracy and reliability of telemedicine for diagnosis of cytomegalovirus retinitis.

PURPOSE: To determine the feasibility of remote diagnostic screening for cytomegalovirus (CMV) retinitis among HIV patients in northern Thailand. DESIGN: Prospective, observational cross-sectional study. METHODS: One hundred eighty-two eyes from 94 consecutive patients with HIV seen in 2008 and 2009 at a tertiary university-based medical center were photographed using a digital retinal camera. Individual and composite images were uploaded to a secure web site. Three expert graders accessed the electronic images and graded each image for signs of CMV retinitis. Results of remote expert grading were compared with on-site patient examination by local expert ophthalmologists. RESULTS: On-site ophthalmologists diagnosed CMV retinitis in 89 (48.9%) of 182 eyes. Trained ophthalmic photographers obtained digital retinal images for all 182 eyes. As compared with the on-site examinations, the sensitivity for detecting CMV retinitis by remote readers using composite retinal images ranged from 89% to 91%. The specificity for detecting CMV retinitis by remote readers ranged from 85% to 88%. Intrarater reliability was high, with each grader achieving a κ value of 0.93. Interrater reliability among the 3 graders also was high, with a κ value of 0.86. CONCLUSIONS: Remote diagnostic screening for CMV retinitis among HIV-positive patients may prove to be a valuable tool in countries where the burden of HIV exceeds the capacity of the local eye care providers to screen for ocular opportunistic infections.