Elham Hatef

Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study.

OBJECTIVES To determine the long-term effects of ranibizumab (RBZ) in patients with diabetic macular edema (DME). DESIGN Prospective, randomized, interventional, multicenter clinical trial. PARTICIPANTS One hundred twenty-six patients with DME. METHODS Subjects were randomized 1:1:1 to receive 0.5 mg RBZ at baseline and months 1, 3, and 5 (group 1), focal or grid laser photocoagulation at baseline and month 3 if needed (group 2), or a combination of 0.5 mg RBZ and focal or grid laser at baseline and month 3 (group 3). Starting at month 6, if retreatment criteria were met, all subjects could be treated with RBZ. MAIN OUTCOME MEASURES The mean change from baseline in best-corrected visual acuity (BCVA) at month 24. RESULTS After the primary end point at month 6, most patients in all groups were treated only with RBZ, and the mean number of injections was 5.3, 4.4, and 2.9 during the 18-month follow-up period in groups 1, 2, and 3, respectively. For the 33 patients in group 1, 34 patients in group 2, and 34 patients in group 3 who remained in the study through 24 months, the mean improvement in BCVA was 7.4, 0.5, and 3.8 letters at the 6-month primary end point, compared with 7.7, 5.1, and 6.8 letters at month 24, and the percentage of patients who gained 3 lines or more of BCVA was 21, 0, and 6 at month 6, compared with 24, 18, and 26 at month 24. The percentage of patients with 20/40 or better Snellen equivalent at month 24 was 45% in group 1, 44% in group 2, and 35% in group 3. Mean foveal thickness (FTH), defined as center subfield thickness, at month 24 was 340 μm, 286 μm, and 258 μm for groups 1, 2, and 3, respectively, and the percentage of patients with center subfield thickness of 250 μm or less was 36%, 47%, and 68%, respectively. CONCLUSIONS Intraocular injections of RBZ provided benefit for patients with DME for at least 2 years, and when combined with focal or grid laser treatments, the amount of residual edema was reduced, as were the frequency of injections needed to control edema. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Wide-field Retinal Imaging in the Management of Noninfectious Posterior Uveitis

PURPOSE To determine whether the use of ultra wide-field imaging changes the management or determination of disease activity in patients with noninfectious posterior uveitis. DESIGN Prospective, observational case series. METHODS setting: Divisions of Retina and Ocular Immunology at single academic medical center. patient population: Total of 43 patients with noninfectious posterior uveitis seen by 4 investigators at the Wilmer Eye Institute. procedures: Each patient underwent standard clinical examination, followed by ultra wide-field scanning laser ophthalmoscope (SLO) imaging and angiography. Investigators successively determined disease activity and management decisions based on clinical examination, examination plus simulated 30- or 60-degree fluorescein angiography (FA) (obtained by physically narrowing the field of view of the wide-field images), examination plus ultra wide-field SLO images, and examination plus wide-field FA. main outcome measures: The primary outcome was the percentage of patients whose management changed based on the availability of wide-field imaging, compared with standard examination and imaging. The secondary outcome was detection of disease activity with and without wide-angle imaging. RESULTS Management was altered in 7 of 43 patients (16%) based on examination and limited FA, whereas 21 of 43 patients (48%) had management change with the use of the ultra wide-field imaging and angiography (P < .001). Disease activity was detected in 22 of 43 patients (51%) based on examination and simulated conventional imaging, and in 27 of 43 (63%) with wide-field imaging (P = .27). CONCLUSIONS The index study, with several design limitations, has suggested that ultra wide-field imaging may alter management decisions compared to standard-of-care imaging and clinical examination. Additional studies, including longitudinal evaluations, are needed to determine whether these findings, or the subsequent management alterations, may improve patient outcomes.

A Cross-sectional Study of the Current Treatment Patterns in Noninfectious Uveitis among Specialists in the United States

PURPOSE Corticosteroids (CS) are the only approved drug class for treatment of noninfectious uveitis by the U.S. Food and Drug Administration. Serious side effects are associated with chronic use of systemic CS; established guidelines recommend the use of steroid-sparing agents if control of uveitis cannot be achieved with ≤ 10 mg/day of prednisone (or equivalent) within 3 months. This study evaluated the treatment patterns among physicians who routinely manage patients with noninfectious uveitis to determine how treatment guidelines are followed. DESIGN Cross-sectional, multicenter study conducted across the United States. PARTICIPANTS Sixty ophthalmologists and 3 rheumatologists were recruited using payer reimbursement International Classification of Diseases, Ninth Revision codes. METHODS Patient data were reported using a study-specific questionnaire. Physicians were also asked if they were aware of or used recommended treatment guidelines. MAIN OUTCOME MEASURES Uveitis treatment patterns were compared with guidelines. RESULTS Physicians managed a mean of 5555 patients; patients with uveitis who required systemic CS treatment comprised approximately 5% of each physicians practice. A total of 580 patients with noninfectious uveitis were randomly selected for analyses. Anterior uveitis requiring systemic therapy was diagnosed in 168 patients (29%), intermediate uveitis was diagnosed in 140 patients (24%), posterior uveitis was diagnosed in 150 patients (26%), and panuveitis was diagnosed in 122 patients (21%); 199 patients (34%) had active disease. The mean time interval from the diagnosis of uveitis to the time of survey was 3.1 to 4.5 years. A systemic disorder was associated with uveitis in 16% to 54% of patients; 57% to 100% of patients received systemic immunosuppressive therapy. In all, 360 of 580 patients (62%) received systemic CS, with a mean initial daily dose of 44 mg, tapered to 34 mg prednisone (or equivalent) as maintenance dose. Among physicians surveyed, 75% did not use or were not aware of treatment guidelines for uveitis. CONCLUSIONS The study reveals that the majority of physicians surveyed are not familiar with or do not adhere to currently recommended guidelines for management of uveitis. High CS doses are used to maintain control of disease, and there is a low level of awareness of recommended guidelines to treat noninfectious uveitis. The finding underscores the need to place further emphasis on educating the medical community and reinforcing treatment guidelines to improve the care of patients with uveitis.

Characterization of macular lesions in punctate inner choroidopathy with spectral domain optical coherence tomography

PurposePunctate inner choroidopathy (PIC) is an ocular inflammatory disease. Spectral domain optical coherence tomography (SD-OCT) allows detailed visualization of retinal and choroidal structures. We aimed to describe the retinal changes on SD-OCT associated with PIC lesions localized in the macula.MethodsRetrospective case series: PIC lesions not associated with choroidal neovascularization (CNV) and captured by macular SD-OCT scans were identified and characterized.ResultsTwenty-seven PIC lesions from seven patients (eight eyes) were identified and classified into four categories according to disease activity and temporal changes. Among clinically inactive patients, two main patterns were noted on OCT: (1) retinal pigment epithelium (RPE) elevation with sub-RPE hyper-reflective signals and (2) localized disruption of outer retinal layers with choroid and Bruchs membrane (BM) generally spared. Clinically active patients demonstrated lesions with intact BM with RPE elevation that fluctuated with disease activity and sub-RPE hyper-reflective signals. Photoreceptor-associated bands on SD-OCT (PRs) were not visible during active disease, but returned to normal visibility when lesions were clinically stable. Seven lesions in patients without clinically detected activity demonstrated alteration of RPE elevation.ConclusionSD-OCT can provide detailed structural characteristics of PIC lesions. RPE elevation is noted in many lesions while BM and choroid are spared. Photoreceptor-associated bands on SD-OCT appear compressed during clinically active stages and are visible during stabilization. OCT may provide information on activity not detected clinically.

Ultra-wide-field retinal imaging in the management of non-infectious retinal vasculitis.

BackgroundThe purpose of this study is to describe and quantify the benefit of ultra-wide-field imaging and fluorescein angiography (FA) in the management of non-infectious retinal vasculitis. In this prospective observational cohort series, patients with non-infectious retinal vasculitis were evaluated and enrolled by four investigators from the Divisions of Retina and Ocular Immunology at the Wilmer Eye Institute. In each patient, disease activity and the need for management changes were assessed, based on clinical examination with or without standard (60°) imaging and then with the addition of ultra-wide-field pseudo-color scanning laser ophthalmoscope (SLO) images and FA using the Optos ultra-wide-field SLO (Optos Panoramic 200MA™, Optos PLC, Dunfermline, Scotland, UK). A standardized questionnaire was completed by each investigator at the time of the clinical evaluation.The primary outcome was the percentage of patients whose management was changed by clinical examination and standard FA, compared with clinical examination plus ultra-wide-field imaging. The secondary outcome was the percentage of patients whose disease was determined to be active based on each modality.ResultsSeventy-one visits from 23 patients were reviewed and analyzed. Based on examination plus ultra-wide-field imaging and ultra-wide-field angiography, disease activity was detected in 48/71 (68%) compared with 32/71 (45%) based on examination and standard FA (P = 0.0095). Based on the clinical examination alone, the decision to alter management was made in 4 of 71 visits (6%), and an additional 3 of 71 (4%) based on simulated standard FA. The addition of ultra-wide-field SLO pseudo-color images altered management in an additional 10/71 visits (14%), and 36/71 (51%) with the addition of ultra-wide-field FA.ConclusionsUltra-wide-field fluorescein imaging and angiography can provide additional information that may be important and relevant in the management of retinal vasculitis.

The relationship between macular sensitivity and retinal thickness in eyes with diabetic macular edema.

PURPOSE To investigate relationship between macular sensitivity and retinal thickness in diabetic macular edema (DME). DESIGN Prospective observational study. METHODS settings: University-based retina practice. patients: Twenty-two eyes of 11 patients with DME. procedure: Fundus microperimetry and retinal thickness tomography were performed simultaneously using an automatic fundus perimetry/tomography system. main outcome measures: Quantification of macular sensitivity, fixation pattern, and relationship between macular sensitivity and retinal thickness. RESULTS Fixation stability revealed that 21 eyes (95.4%) had stable fixation (>75% within central 2 degrees of point of fixation) and 1 eye (4.5%) had relatively unstable fixation (<75% of fixation points located within 2 degrees, >75% located within 4 degrees). Evaluation of fixation location revealed that 15 eyes (68.2%) had central (>50% of fixation points within 0.5 mm of fovea), 3 eyes (13.6%) pericentral (25% to 50% within 0.5 mm of fovea), and 4 eyes (18.2%) eccentric (<25% of fixation points within 0.5 mm of fovea) fixation location. Macular sensitivity increased by an average of 0.03 decibel (dB) (95% confidence interval [CI]: 0.00, 0.06) per 1-micron (μm) increase in retinal thickness for thickness values ≤280 μm measured with the OPKO/OTI spectral-domain OCT. The macular sensitivity decreased by an average 0.05 dB (95% CI: -0.08, -0.02) per 1-μm increase in thickness for thickness values >280 μm. CONCLUSIONS In this pilot study, the majority of eyes with DME had stable, central fixation. Macular sensitivity varied depending on the thickness of the retina. Additional studies are needed to determine the role of microperimetry in eyes with DME.

Association of Retinal Sensitivity to Integrity of Photoreceptor Inner/Outer Segment Junction in Patients with Diabetic Macular Edema

PURPOSE To evaluate the relationship between retinal sensitivity and the photoreceptor inner segment/outer segment (IS/OS) layer status in patients with diabetic macular edema (DME). DESIGN Cross-sectional study. PARTICIPANTS Twenty-five adult patients (37 eyes) diagnosed with DME and managed at the Wilmer Eye Institute, Johns Hopkins University (Baltimore, MD). METHODS We obtained simultaneous fundus microperimetry (MP) and optical coherence tomography (OCT) of patients with DME using a combined MP/OCT system. The device recorded retinal sensitivity and retinal thickness on a 3-dimensional tomography map, and we performed a point-by-point analysis of the IS/OS layer integrity at every MP point. We also reviewed OCT scans to determine the type of DME, cystoid macular edema, or diffuse macular edema (absence of any cysts). In addition, fixation stability and fixation location were analyzed. MAIN OUTCOME MEASURES Retinal point sensitivity measured by MP. RESULTS Twenty-five patients (37 eyes: 29 male and 8 female; mean age, 64.16 years) with DME were enrolled. Fixation was centric in 30 eyes (81%), paracentric in 3 eyes (8%), and eccentric in 4 eyes (11%). Twenty-seven eyes had cystoid macular edema, and 10 eyes had diffuse macular edema. Mean central subfield thickness was 325 μm. We analyzed a total of 1036 individual MP points. Mean point sensitivity was 10.51 dB. A total of 793 points (76.5%) had IS/OS layer present, and 243 points (23.5%) had IS/OS layer disrupted. A mixed linear model, constructed to adjust for potential confounders and account for dependence between retinal points, revealed that the absence of the IS/OS junction was significantly associated with a 3.28-dB decrease in retinal point sensitivity (P<0.001). CONCLUSIONS This novel index study demonstrates that disruption of the IS/OS junction is correlated with a significant decrease in point sensitivity in eyes with DME. Further studies are indicated to confirm and validate this relationship. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Spectral- and time-domain optical coherence tomography measurements of macular thickness in normal eyes and in eyes with diabetic macular edema

PurposeTo report macular thickness values in normal eyes and eyes with diabetic macular edema (DME) using time-domain (TD) and spectral-domain (SD) optical coherence tomography (OCT), and to derive a conversion equation.MethodsThe index study was a prospective investigation conducted on 80 eyes from 40 normal subjects and 130 eyes from 118 patients with DME seen in our clinic. Retinal thickness values from the central 1 mm of the macula and surrounding four ETDRS subfields were acquired using TD-OCT (Stratus OCT) and SD-OCT (SPECTRALIS HRA+OCT). Measurements of the central (C) subfield from both devices were used to derive a conversion equation. The equation was used to predict SD-OCT values using measurements from TD-OCT. Agreement between predicted and actual SD-OCT measurements was assessed.ResultsIn normal eyes, the mean difference between TD-OCT and SD-OCT measurements of the C subfield was 76 μm (CI95=74 and 77, respectively). The conversion equation, y=1.029x+72.49, was derived. In eyes with DME, using the equation, SPECTRALIS-predicted values were 5% higher than actual measurements, with 95% of predicted values falling within 9% of the actual measurements. Relocating SD-OCT grids to match the location on TD-OCT resulted in predicted values falling within 7% of actual measurements.ConclusionsThe percent difference between actual thickness measurements from SPECTRALIS and predicted thickness measurements, using the conversion equation, was within reported limits of repeatability of Stratus in eyes with DME. Our equation may help correlate OCT values from both devices in standard care and clinical trials for DME.

Mycophenolate mofetil and fundus autofluorescence in the management of recurrent punctate inner choroidopathy.

Purpose: To compare the frequencies of attacks before and after immunomodulatory therapy (IMT) with mycophenolate mofetil (MMF) in recurrent punctate inner choroidopathy (PIC) and to report fundus autofluorescence (FAF) findings. Methods: Eight patients who had at least two recurrent episodes of increased activity before MMF and 12 months of documented clinical course before and after MMF were included. The frequencies of attacks before and after MMF were compared. FAF images evaluated. Results: Before MMF, the 8 patients experienced 19 attacks of recurrent disease activity; during MMF therapy, 3 (38%) patients experienced 6 recurrent episodes. The attack frequencies were 1.09 ± 0.75 before and 0.23 ± 0.32 during treatment (p = .036). Among the 6 patients who had FAF, surrounding hyperautofluorescent halo was detected in 4 and recurrence occurred in 2 who did not show any changes on the intensity during treatment. Conclusion: In the index study, the employment of MMF has decreased frequency of attacks in recurrent PIC. FAF may be employed to monitor and predict the response to treatment.

Comparison of time domain and spectral domain optical coherence tomography in measurement of macular thickness in macular edema secondary to diabetic retinopathy and retinal vein occlusion.

Purpose. To evaluate macular thickness, agreement, and intraclass repeatability in three optical coherence tomography (OCT) devices: the time domain (TD) Stratus OCT and two spectral domain (SD) OCTs, Spectralis and Cirrus SD-OCT, in eyes with macular edema secondary to diabetic retinopathy (DR) and retinal vein occlusion (VO). Methods. In a prospective observational study at a university-based retina practice, retinal thickness tomography was performed simultaneously for fifty-eight patients (91 eyes) with DR and VO employing a time domain and two spectral domain OCTs. Agreement in macular measurements was assessed by constructing Bland-Altman plots. Intraclass repeatability was assessed by intraclass correlation coefficients (ICCs). Results. Based on the Bland-Altman plots for central macular thickness, there was low agreement between the measurements of Cirrus SD-OCT and Stratus OCT, Spectralis OCT and Stratus OCT, as well as Spectralis OCT and Cirrus SD-OCT among DR and RVO patients. All three devices demonstrated high intraclass repeatability, with ICC of 98% for Stratus OCT, 97% for Cirrus SD-OCT, and 100% for Spectralis OCT among DR patients. The ICC was 97% for Stratus OCT, 79% for Cirrus SD-OCT, and 91% for Spectralis OCT among RVO patients. Conclusion. There are low agreements among interdevice measurements. However, intraclass repeatability is high in both TD and SD-OCT devices.