Naira Khachatryan

Rates of retinal nerve fiber layer thinning in glaucoma suspect eyes

PURPOSE To compare the rates of retinal nerve fiber layer (RNFL) loss in patients suspected of having glaucoma who developed visual field damage (VFD) with those who did not develop VFD and to determine whether the rate of RNFL loss can be used to predict the development of VFD. DESIGN Prospective, observational cohort study. PARTICIPANTS Glaucoma suspects, defined as having glaucomatous optic neuropathy or ocular hypertension (intraocular pressure, >21 mmHg) without repeatable VFD at baseline, from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. METHODS Global and quadrant RNFL thickness (RNFLT) were measured with the Spectralis spectral-domain optical coherence tomography (SD-OCT; Spectralis HRA+OCT [Heidelberg Engineering, Heidelberg, Germany]). Visual field damage was defined as having 3 consecutive abnormal visual fields. The rate of RNFL loss in eyes developing VFD was compared to eyes not developing VFD using multivariate linear mixed-effects models. A joint longitudinal survival model used the estimated RNFLT slope to predict the risk of developing VFD, while adjusting for potential confounding variables. MAIN OUTCOME MEASURES The rate of RNFL thinning and the probability of developing VFD. RESULTS Four hundred fifty-four eyes of 294 glaucoma suspects were included. The average number of SD-OCT examinations was 4.6 (range, 2-9), with median follow-up of 2.2 years (0.4-4.1 years). Forty eyes (8.8%) developed VFD. The estimated mean rate of global RNFL loss was significantly faster in eyes that developed VFD compared with eyes that did not develop VFD (-2.02 μm/year vs. -0.82 μm/year; P<0.001). The joint longitudinal survival model showed that each 1-μm/year faster rate of global RNFL loss corresponded to a 2.05-times higher risk of developing VFD (hazard ratio, 2.05; 95% confidence interval, 1.14-3.71; P = 0.017). CONCLUSIONS The rate of global RNFL loss was more than twice as fast in eyes that developed VFD compared with eyes that did not develop VFD. A joint longitudinal survival model showed that a 1-μm/year faster rate of RNFLT loss corresponded to a 2.05-times higher risk of developing VFD. These results suggest that measuring the rate of SD-OCT RNFL loss may be a useful tool to help identify patients who are at a high risk of developing visual field loss.

Diagnostic Accuracy of the Spectralis and Cirrus Reference Databases in Differentiating between Healthy and Early Glaucoma Eyes.

PURPOSE To evaluate and compare the diagnostic accuracy of global and sector analyses for detection of early visual field (VF) damage using the retinal nerve fiber layer (RNFL) reference databases of the Spectralis (Heidelberg Engineering, Heidelberg, Germany) and Cirrus (Carl Zeiss Meditec, Dublin, CA) spectral-domain optical coherence tomography (SD OCT) devices. METHODS Healthy subjects and glaucoma suspects from the Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES) with at least 2 years of follow-up were included. Global and sectoral RNFL measures were classified as within normal limits, borderline (BL), and outside normal limits (ONL) on the basis of the device reference databases. The sensitivity of ONL classification was estimated in glaucoma suspect eyes that developed repeatable VF damage. RESULTS A total of 353 glaucoma suspect eyes and 279 healthy eyes were included. A total of 34 (9.6%) of the glaucoma suspect eyes developed VF damage. In glaucoma suspect eyes, Spectralis and Cirrus ONL classification was present in 47 eyes (13.3%) and 24 eyes (6.8%), respectively. The sensitivity of the global RNFL ONL classification among eyes that developed VF damage was 23.5% for Cirrus and 32.4% for Spectralis. The specificity of within-normal-limits global classification in healthy eyes was 100% for Cirrus and 99.6% for Spectralis. There was moderate to substantial agreement between Cirrus and Spectralis classification as ONL. CONCLUSIONS The Spectralis and Cirrus reference databases have a high specificity for identifying healthy eyes and good agreement for detection of eyes with early glaucoma damage.

Rate and Pattern of Rim Area Loss in Healthy and Progressing Glaucoma Eyes

PURPOSE To characterize the rate and pattern of age-related and glaucomatous neuroretinal rim area changes in subjects of African and European descent. DESIGN Prospective longitudinal study. PARTICIPANTS Two hundred ninety-six eyes of 157 healthy subjects (88 patients of African descent and 69 of European descent) and 73 progressing glaucoma eyes of 67 subjects (24 patients of African descent and 43 of European descent) from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study were included. METHODS Global and sectoral rim areas were measured using confocal laser scanning ophthalmoscopy. Masked stereophotograph review determined progression of glaucomatous optic disc damage. The rates of absolute rim area loss and percentage rim area loss in healthy and progressing glaucomatous eyes were compared using multivariate, nested, mixed-effects models. MAIN OUTCOME MEASURES Rate of rim area loss over time. RESULTS The median follow-up time was 5.0 years (interquartile range, 2.0-7.4 years) for healthy eyes and 8.3 years (interquartile range, 7.5-9.9 years) for progressing glaucoma eyes. The mean rate of global rim area loss was significantly faster in progressing glaucomatous eyes compared with healthy eyes for both rim area loss (-10.2×10(-3) vs. -2.8×10(-3) mm(2)/year, respectively; P < 0.001) and percentage rim area loss (-1.1% vs. -0.2%/year, respectively; P < 0.001), but considerable overlap existed between the 2 groups. Sixty-three percent of progressing glaucoma eyes had a rate of change faster than the fifth quantile of healthy eyes. For both healthy and progressing eyes, the pattern of rim area loss and percentage rim area loss were similar, tending to be fastest in the superior temporal and inferior temporal sectors. The rate of change was similar in progressing eyes of patients of African or European descent. CONCLUSIONS Compared with healthy eyes, the mean rate of global rim area loss was 3.7 times faster and the mean rate of global percentage rim area loss was 5.4 times faster in progressing glaucoma eyes. A reference database of healthy eyes can be used to help clinicians distinguish age-related rim area loss from rim area loss resulting from glaucoma.

Risk of Ocular Hypertension in Adults with Noninfectious Uveitis

PURPOSE To describe the risk and risk factors for ocular hypertension (OHT) in adults with noninfectious uveitis. DESIGN Retrospective, multicenter, cohort study. PARTICIPANTS Patients aged ≥18 years with noninfectious uveitis seen between 1979 and 2007 at 5 tertiary uveitis clinics. METHODS Demographic, ocular, and treatment data were extracted from medical records of uveitis cases. MAIN OUTCOME MEASURES Prevalent and incident OHT with intraocular pressures (IOPs) of ≥21 mmHg, ≥30 mmHg, and increase of ≥10 mmHg from documented IOP recordings (or use of treatment for OHT). RESULTS Among 5270 uveitic eyes of 3308 patients followed for OHT, the mean annual incidence rates for OHT ≥21 mmHg and OHT ≥30 mmHg are 14.4% (95% confidence interval [CI], 13.4-15.5) and 5.1% (95% CI, 4.7-5.6) per year, respectively. Statistically significant risk factors for incident OHT ≥30 mmHg included systemic hypertension (adjusted hazard ratio [aHR], 1.29); worse presenting visual acuity (≤20/200 vs. ≥20/40, aHR, 1.47); pars plana vitrectomy (aHR, 1.87); history of OHT in the other eye: IOP ≥21 mmHg (aHR, 2.68), ≥30 mmHg (aHR, 4.86) and prior/current use of IOP-lowering drops or surgery in the other eye (aHR, 4.17); anterior chamber cells: 1+ (aHR, 1.43) and ≥2+ (aHR, 1.59) vs. none; epiretinal membrane (aHR, 1.25); peripheral anterior synechiae (aHR, 1.81); current use of prednisone >7.5 mg/day (aHR, 1.86); periocular corticosteroids in the last 3 months (aHR, 2.23); current topical corticosteroid use [≥8×/day vs. none] (aHR, 2.58); and prior use of fluocinolone acetonide implants (aHR, 9.75). Bilateral uveitis (aHR, 0.69) and previous hypotony (aHR, 0.43) were associated with statistically significantly lower risk of OHT. CONCLUSIONS Ocular hypertension is sufficiently common in eyes treated for uveitis that surveillance for OHT is essential at all visits for all cases. Patients with 1 or more of the several risk factors identified are at particularly high risk and must be carefully managed. Modifiable risk factors, such as use of corticosteroids, suggest opportunities to reduce OHT risk within the constraints of the overriding need to control the primary ocular inflammatory disease.

Immunosuppressive Therapy and Cancer Risk in Ocular Inflammation Patients: Fresh Evidence and More Questions

Although there is strong scientific evidence indicating the effectiveness of immunosuppression for severe ocular inflammatory disease, patients and health care providers often ask whether the benefits of systemic immunosuppressive therapy warrant potentially associated risks. The risk of developing a significant illness, such as cancer, is of particular interest. Accurate information about the longterm risks associated with immunosuppressive therapy is needed to inform clinical decision making and develop standards of care for these patients. Because clinical trials typically do not have sufficient sample sizes and durations of follow-up to detect such adverse events, much of the evidence available must come from the studies that are, by design, observational. Observational studies potentially are subject to indications-for-treatment bias: the