Longitudinal Changes in Scotopic and Mesopic Macular Function as Assessed with Microperimetry in Patients With Stargardt Disease: SMART Study Report No. 2.

PURPOSE: To estimate and compare cross-sectional scotopic versus mesopic macular sensitivity losses measured by microperimetry, and to report and compare the longitudinal rates of scotopic and mesopic macular sensitivity losses in ABCA4 gene-associated Stargardt disease (STGD1). DESIGN: This was a multicenter prospective cohort study. METHODS: Participants comprised 127 molecularly confirmed STGD1 patients enrolled from 6 centers in the United States and Europe and followed up every 6 months for up to 2 years. The Nidek MP-1S device was used to measure macular sensitivities of the central 20° under mesopic and scotopic conditions. The mean deviations (MD) from normal for mesopic macular sensitivity for the fovea (within 2° eccentricity) and extrafovea (4°-10° eccentricity), and the MD for scotopic sensitivity for the extrafovea, were calculated. Linear mixed effects models were used to estimate mesopic and scotopic changes. Main outcome measures were baseline mesopic mean deviation (mMD) and scotopic MD (sMD) and rates of longitudinal changes in the mMDs and sMD. RESULTS: At baseline, all eyes had larger sMD, and the difference between extrafoveal sMD and mMD was 10.7 dB (P < .001). Longitudinally, all eyes showed a statistically significant worsening trend: the rates of foveal mMD and extrafoveal mMD and sMD changes were 0.72 (95% CI = 0.37-1.07), 0.86 (95% CI = 0.58-1.14), and 1.12 (95% CI = 0.66-1.57) dB per year, respectively. CONCLUSIONS: In STGD1, in extrafovea, loss of scotopic macular function preceded and was faster than the loss of mesopic macular function. Scotopic and mesopic macular sensitivities using microperimetry provide alternative visual function outcomes for STGD1 treatment trials.

Blue light versus green light fundus autofluorescence in normal subjects and in patients with retinochoroidopathy secondary to retinal and uveitic diseases.

PURPOSE: The aim of this study is to evaluate the differences in the fundus autofluorescence (FAF) signal between the blue light autofluorescence (BAF) from Spectralis® (Heidelberg, CA) and green light autofluorescence (GAF) 200TxTM (OPTOS, UK, in normal subjects and in patients with retinochoroidopathies (RC). METHODS: In this prospective study, FAF was performed using BL (λ = 488 nm) and GL (λ = 532 nm) on normal subjects and patients with RC. The corresponding pairs of BAF and GAF images from both groups were analyzed using Photoshop. The strength of the FAF signal was measured on a gray scale, where optic disc was a standard to indicate absence of AF. In addition, gray values obtained from three identical points (foveal center, and points of hypo and hyper autofluorescence) in the corresponding BAF and GAF images of normal and RC subjects were divided by the optic disc value to calculate autofluorescence signal ratio (R). The R values at fovea (R1), hypoautofluorescent point (R2), and hyperautofluorescent point (R3) were compared between BAF and GAF modalities, in normal and in RC subjects separately. RESULTS: One hundred six pairs (106 eyes) of FAF images analyzed (37 pairs: normal and 69 pairs: RC subjects). In normal subjects, the mean R1, R2, and R3 values for BAF were (1.5 ± 0.88, 1.23 ± 0.58, and 4.73 ± 2.85, respectively) and for GAF were (0.78 ± 0.20, 0.78 ± 0.20, and 1.62 ± 0.39, respectively). Similarly, in subjects with RC, the mean R1, R2, and R3 values for BAF were (1.68 ± 1.02, 1.66 ± 1.15, and 7.75 ± 6.82, respectively) and for GAF were (0.95 ± 0.59, 0.79 ± 0.45, and 2.50 ± 1.65, respectively). The mean difference in the R1, R2, and R3 ratios between BAF and GAF in normal and in RC subjects was statistically significant (p < 0.001). The strength of the correlation (r) between ratios for BAF and GAF was weak or not statistically significant in both normal and RC subjects (p > 0.05). CONCLUSION: The distribution and intensity of the AF signal differ in BAF and GAF and cannot be used interchangeably. In BAF, optic disc signal is always weaker than in other areas, which was not true for GAF where optic disc signal was stronger than fovea and hypoautofluorescent point in both groups.

Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART) Study: Design and Baseline Characteristics (Report No. 1).

PURPOSE: To describe the study design and characteristics at first visit of participants in the longitudinal Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART) study. METHODS: Scotopic microperimetry (sMP) was performed in one designated study eye in a subset of participants with molecularly proven ABCA4-associated Stargardt disease (STGD1) enrolled in a multicenter natural history study (ProgStar). Study visits were every 6 months over a period ranging from 6 to 24 months, and also included fundus autofluorescence (FAF). RESULTS: SMART enrolled 118 participants (118 eyes). At the first visit of SMART, the mean sensitivity in mesopic microperimetry was 11.48 (±5.05; range 0.00-19.88) dB and in sMP 11.25 (±5.26; 0-19.25) dB. For FAF, all eyes had a lesion of decreased autofluorescence (mean lesion size 3.62 [±3.48; 0.10-21.46] mm2), and a total of 76 eyes (65.5%) had a lesion of definitely decreased autofluorescence with a mean lesion size of 3.46 (±3.60; 0.21-21.46) mm2. CONCLUSIONS: Rod function is impaired in STGD1 and can be assessed by sMP. Testing rod function may serve as a potential outcome measure for future clinical treatment trials. This is evaluated in the SMART study.

The Progression of the Stargardt Disease Type 4 (ProgStar-4) Study: Design and Baseline Characteristics (ProgStar-4 Report No. 1).

BACKGROUND/AIMS: To describe the design and baseline characteristics of patients enrolled in the multicenter, prospective natural history study of Stargardt disease type 4. METHODS: Fifteen eligible patients aged 6 years and older at baseline, harboring disease-causing variants in the PROM1 gene, and with specified ocular lesions were enrolled. They were examined at baseline using a standard protocol, with 6 monthly follow-up visits for a 2-year period including best-corrected ETDRS visual acuity, spectral-domain optical coherence tomography, fundus autofluorescence (FAF), mesopic and scotopic microperimetry (MP). Areas of definitely decreased FAF (DDAF) and questionably decreased FAF were outlined and quantified on FAF images. RESULTS: Amongst the 15 patients (29 eyes) that were enrolled at 5 centers in the USA and Europe, 10 eyes (34.5%) had areas of DDAF with an average lesion area of 3.2 ± 3.5 mm2 (range 0.36-10.39 mm2) at baseline. The mean retinal sensitivity of the posterior pole derived from mesopic MP was 8.8 ± 5.8 dB. CONCLUSIONS: Data on disease progression in PROM1-related retinopathy from this study will contribute to the characterization of the natural history of disease and the exploration of the utility of several modalities to track progression and therefore to potentially be used in future interventional clinical trials.

Assessment of estimated retinal atrophy progression in Stargardt macular dystrophy using spectral-domain optical coherence tomography.

AIMS: To estimate disease progression based on analysis of macular volume measured by spectral-domain optical coherence tomography (SD-OCT) in patients affected by Stargardt macular dystrophy (STGD1) and to evaluate the influence of software errors on these measurements. METHODS: 58 eyes of 29 STGD1 patients were included. Numbers and types of algorithm errors were recorded and manually corrected. In a subgroup of 36 eyes of 18 patients with at least two examinations over time, total macular volume (TMV) and volumes of all nine Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields were obtained. Random effects models were used to estimate the rate of change per year for the population, and empirical Bayes slopes were used to estimate yearly decline in TMV for individual eyes. RESULTS: 6958 single B-scans from 190 macular cube scans were analysed. 2360 (33.9%) showed algorithm errors. Mean observation period for follow-up data was 15 months (range 3-40). The median (IQR) change in TMV using the empirical Bayes estimates for the individual eyes was -0.103 (-0.145, -0.059) mm3 per year. The mean (±SD) TMV was 6.321±1.000 mm3 at baseline, and rate of decline was -0.118 mm3 per year (p=0.003). Yearly mean volume change was -0.004 mm3 in the central subfield (mean baseline=0.128 mm3), -0.032 mm3 in the inner (mean baseline=1.484 mm3) and -0.079 mm3 in the outer ETDRS subfields (mean baseline=5.206 mm3). CONCLUSIONS: SD-OCT measurements allow monitoring the decline in retinal volume in STGD1; however, they require significant manual correction of software errors.

Assessment of changes in quality of life among patients in the SAVE Study - Sirolimus as therapeutic Approach to uVEitis: a randomized study to assess the safety and bioactivity of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis.

BACKGROUND: The National Eye Institute 39-Question Visual Function Questionnaire (NEI VFQ-39) is an indicator of vision-related quality of life (QoL). The NEI VFQ-39 is used to assess the QoL in patients with non-infectious posterior uveitis, intermediate uveitis, or panuveitis, treated with subconjunctival (SCJ) or intravitreal (IVT) sirolimus as an immunomodulatory therapeutic (IMT) agent, delivered subconjunctivally (SCJ) or intravitreally (IVT) (the SAVE Study). Thirty subjects with non-infectious uveitis were randomized (SCJ:IVT, 1:1) for a prospective clinical trial. The 39-Question Visual Function Questionnaire (VFQ-39) was administered at baseline (BL), month 6 (M6), and month 12 (M12) visits. The survey measures self-reported vision health status for patients with chronic eye disease and assesses the effects of visual impairment on both task-oriented visual function and general health domains. In accordance to the NEI-VFQ Manual, each patient's questionnaire was converted to a scaled score between 0 (worst) and 100 (best), and median scores were calculated for each of the subcategories and overall composite score at BL, M6, and M12. Wilcoxon signed-rank test was performed. RESULTS: Twenty-six patients completed the VFQ-39 at BL and M6, whereas 23 patients completed it at M12. Patients showed a significant improvement in pooled composite scores from BL to M6 and BL to M12. Analysis by treatment groups showed that intravitreal injection of sirolimus is better tolerated. CONCLUSIONS: Sirolimus has demonstrated bioactivity as an IMT and corticosteroid-sparing agent to treat non-infectious uveitis. Patients receiving intravitreal injection of sirolimus showed overall improvement of vision-related health while those receiving subconjunctival injections did not. Larger randomized control trials with sirolimus are indicated to validate these results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00908466.

Fixation Stability Measurement Using Two Types of Microperimetry Devices.

PURPOSE: We compared the fixation stability measurements obtained with two microperimeters, the Micro Perimeter 1 (MP-1) and the Spectral OCT/SLO (OCT/SLO), in subjects with and without maculopathies. METHODS: A total of 41 eyes with no known ocular diseases and 45 eyes with maculopathies were enrolled in the study. Both eyes of each participant had a 20-second fixation test using the MP-1 and OCT/SLO. The bivariate contour ellipse area (BCEA) was used for fixation stability evaluation. RESULTS: In the normal group, BCEA was 2.93 ± 0.32 log minarc2 on OCT/SLO and 2.89 ± 0.30 log minarc2 on MP-1. In the maculopathy group, BCEA was 3.05 ± 0.41 log minarc2 on OCT/SLO and 3.15 ± 0.46 log minarc2 on MP-1. There was no statistically significant difference between the BCEA measured by OCT/SLO and by MP-1 in both groups. A moderate correlation was found between the two devices (r = 0.45, P < 0.001). The sample size during the fixation test was 535.5 ± 14.6 pairs of coordinates in the normal group and 530.7 ± 14.9 pairs in the maculopathy group with MP-1, while it was 72.3 ± 6.9 and 59.9 ± 10.1, respectively, with OCT/SLO. This was due to different tracking frequencies between the two microperimeters. CONCLUSION: Fixation stability assessment yields similar results using the OCT/SLO and MP-1. A major difference in sampling rate between the two microperimeters does not significantly affect BCEA measurements. TRANSLATIONAL RELEVANCE: Fixation stability assessments are comparable and interchangeable between the OCT/SLO and the MP-1.

One-Year Outcomes of the SAVE Study: Sirolimus as a Therapeutic Approach for UVEitis.

PURPOSE: To determine the efficacy and safety of repeated intravitreal and subconjunctival administrations of sirolimus in patients with noninfectious uveitis at 1 year in the Sirolimus as a Therapeutic Approach UVEitis (SAVE) Study. METHODS: Open-label, prospective, and randomized interventional clinical trial in which 30 patients with noninfectious intermediate, posterior, or panuveitis were randomized 1:1 to receive sirolimus 352-µg intravitreal or 1320-µg subconjunctival. Sirolimus was administered at days 0, 60, and 120. At month 6, all subjects were allowed to receive sirolimus at intervals greater than or equal to 2 months and until month 12. Changes in vitreous haze (VH), visual acuity (VA), and retinal thickness at month 12 were compared with baseline. RESULTS: Of patients with active uveitis at baseline (n = 20), 70% showed greater than or equal to 2 steps reduction of VH at month 12 (P < 0.05), 88% (n = 7) of patients with inactive uveitis at baseline showed either no change or reduction of VH to no haze, 36% (n = 10) of all patients (n = 28) gained greater than or equal to one line of VA, 21% (n = 6) lost greater than or equal to 1 line, and 43% (n = 12) showed no change. At the end of 1 year, no statistical differences in efficacy were found between intravitreal and subconjunctival groups. No serious adverse events were determined to be secondary to sirolimus. CONCLUSIONS: Repeated subconjunctival/intravitreal injections of sirolimus appear to be tolerated by patients with noninfectious uveitis over 12 months. Results from the index study suggest that sirolimus may provide benefits to patients with uveitis. Both intravitreal and subconjunctival routes demonstrate similar bioactivity/efficacy. The intravitreal route, however, was better tolerated. TRANSLATIONAL RELEVANCE: The SAVE Study illustrates for the first time the application of local formulations of sirolimus in non-infectious intermediate, posterior, and pan-uveitis. Subconjunctival/Intravitreal sirolimus may help to control inflammation while offering better tolerability/safety profiles than systemic therapies, including immunosuppressants and corticosteroids.

Retinal sensitivity is a valuable complementary measurement to visual acuity--a microperimetry study in patients with maculopathies.

PURPOSE: To evaluate changes in macular sensitivity, as measured with microperimetry, among patients with maculopathy and stable visual acuity (VA). METHODS: Macular sensitivity was assessed using the Spectral OCT/SLO™ microperimetry (OCT/SLO, Optos Plc., Dunfermline, UK) in 25 eyes (16 patients) with maculopathy and stable VA (<5 letters change in ETDRS score) at two consecutive clinic visits. To take the limits of the test-retest repeatability of the OCT/SLO into account, coefficient of repeatability (CoR) was employed to estimate the probability of the sensitivity changes being secondary to measurement noise. RESULTS: The point sensitivity changes were statistically significant (Wilcoxon signed-rank test, P < 0.001). Seventy-seven points (11 %) out of a total of 700 sensitivity points had a genuine sensitivity change, with a mean increase of 8.6 ± 2.6 dB in 35 points and a mean decrease of 7.9 ± 2.2 dB in 42 points. CONCLUSIONS: Point-to-point change in macular sensitivity can be used as a biomarker of changes in disease activity in patients with maculopathy, and can be more accurate than either mean sensitivity or BCVA in detection of changes in macular function. The measurement variability should be considered when observing the local sensitivity changes.

Assessment of oxygen saturation in retinal vessels of normal subjects and diabetic patients with and without retinopathy using Flow Oximetry System.

PURPOSE: To assess oxygen saturation (StO2) in retinal vessels of normal subjects and diabetic patients with and without retinopathy using the modified version of the Flow Oximetry System (FOS) and a novel assessment software. METHODS: The FOS and novel assessment software were used to determine StO2 levels in arteries and veins located between 1 and 2 mm from the margin of the optic disc and in the macular area. RESULTS: Eighteen normal subjects, 15 diabetics without diabetic retinopathy (DM no DR), and 11 with non-proliferative diabetic retinopathy (NPDR) were included in final analysis. The mean [± standard deviation (SD)] StO2 in retinal arteries was 96.9%±3.8% in normal subjects; 97.4%±3.7% in DM no DR; and 98.4%±2.0% in NPDR. The mean venous StO2 was 57.5%±6.8% in normal subjects; 57.4%±7.5% in DM no DR; and 51.8%±6.8% in NPDR. The mean arterial and venous StO2 across the three groups were not statistically different (P=0.498 and P=0.071, respectively). The arterio-venous differences between the three study groups, however, were found to be statistically significant (P=0.015). Pairwise comparisons have demonstrated significant differences when comparing the A-V difference in the NPDR group to either normal subjects (P=0.02) or diabetic patients without DR (P=0.04). CONCLUSIONS: The arterio-venous difference was greater, and statistically significant, in patients with NPDR when compared to normal subjects and to patients with diabetes and no retinopathy. The mean venous StO2 was lower, but not statistically significant, in NPDR compared with diabetics without retinopathy and with normal subjects.

A randomized controlled trial of panretinal photocoagulation with and without intravitreal ranibizumab in treatment-naive eyes with non-high-risk proliferative diabetic retinopathy.

PURPOSE: To compare the efficacy of panretinal photocoagulation (PRP) and intravitreal ranibizumab injection with PRP alone in patients with treatment-naive bilateral non-high-risk proliferative diabetic retinopathy. METHODS: Sixty eyes of 30 patients were randomized either to the study group (SG) receiving PRP plus 2 ranibizumab injections or to the control group (CG) receiving PRP alone. Mean change in best-corrected visual acuity and in optical coherence tomography were compared at baseline and 1, 3, and 6 months. RESULTS: Best-corrected visual acuity was significantly better at 6 months in the SG; however, there was decrease in best-corrected visual acuity in the CG. Central macula thickness decreased significantly at 6 months in SG when compared with baseline (-47.6 µm, P < 0.001) and did not reveal significant difference in the CG. In eyes with diabetic macular edema, best-corrected visual acuity increased by 3.6 letters (P = 0.06) in the SG and decreased by 4.4 letters in the CG (P = 0.003). Central macula thickness decreased by 69.3 µm (P = 0.001) in the SG and decreased by 45.5 µm (P = 0.11) in the CG. CONCLUSION: Intravitreal ranibizumab in combination with PRP can be an effective treatment in eyes with non-high-risk proliferative diabetic retinopathy and diabetic macular edema.

Assessment of Central Retinal Sensitivity Employing Two Types of Microperimetry Devices.

PURPOSE: To compare the retinal sensitivity measurements obtained with two microperimeters, the Micro-Perimeter 1 (MP-1) and the Optos optical coherence tomography (OCT)/scanning laser ophthalmoscope (SLO) in subjects with and without maculopathies. METHODS: Forty-five eyes with no known ocular disease and 47 eyes with maculopathies were examined using both microperimeters. A contrast-adjusted scale was applied to resolve the different stimuli and background luminance existing between the two devices. RESULTS: There was a strong ceiling effect with the MP-1 in the healthy group, with 90.1% (1136 of 1260) test points clustered at 20 dB. The mean sensitivity for the corresponding points in the OCT/SLO was 25.8 ± 1.9 dB. A floor effect was also observed with the OCT/SLO in the maculopathy group with 9.7% (128 of 1316) points clustered at 9-dB values. The corresponding mean sensitivity in the MP-1 was 1.7 ± 3.9 dB. A regression equation between the two microperimeters was established in the common 10 to19 dB intervals as: OCT/SLO = 15.6 + 0.564 × MP-1 - 0.009 × MP-12 + k (k is an individual point constant; MP-1 coefficient P < 0.001; MP-12 coefficient P = 0.006). CONCLUSION: The OCT/SLO and the MP-1 provide two different ranges of contrasts for microperimetry examination. Broadening the dynamic range may minimize the constraint of the ceiling and floor effect. There is a significant mathematical relationship in the common interval of the contrast scale. TRANSLATIONAL RELEVANCE: Applying a unified and broadened dynamic range in different types of microperimeters will help to generate consistent clinical reference for measurements.

Variation of choroidal thickness and vessel diameter in patients with posterior non-infectious uveitis.

BACKGROUND: Choroidal thickness (CTh) and choroidal vessel diameter (VD) in the Haler's layer were evaluated as markers of inflammatory insult in non-infectious uveitis (NIU). Spectral-domain optical coherence tomography (Spectralis®, Heidelberg Engineering Inc.) scans were acquired from 23 normal subjects (39 eyes - group 1), 7 subjects with high myopia (14 eyes - group 2), and 19 patients with NIU (23 eyes - group 3). In groups 1 and 2, CTh and VD were measured at 3 different points of the same horizontal OCT scan passing through the fovea and a mean calculated. Mean CTh and VD were calculated in 2 other locations, 2 mm superior and inferior from the chosen foveal horizontal scan. In group 3, three measurements of CTh and VD were obtained within 1 mm of a horizontal scan passing through a retinal lesion; mean CTh and VD were then computed. A ratio (R) between the VD and the corresponding CTh was calculated. RESULTS: Group 1, 2 and 3 mean age was 29.6, 29.1 and 45.9 years, respectively. Sixteen normal subjects, three myopic subjects and six NIU patients were male.. Group 1 mean CTh did not differ from group 2 (261.6±45.6 vs. 260.2±50.6 µm µm; p>0.05); mean VD was marginally higher in Group 2 (159.8±32.2 vs. 163.2±33.2 µm; p>0.05). Group 3 demonstrated thinner CTh (193.6±54.6 µm) than Groups 1 and 2 (p = 0.02 and <0.001). Group 3 mean VD (123.6±37.4 µm) was also less than that in Groups 1 and 2; the difference was statistically significant only when compared to group 2, p = 0.01. R did not differ across groups (p-values >0.05), indicating that variations in CTh and VD followed the same trend. CONCLUSIONS: The study reports potential quantitative OCT-derived parameters that may be explored in future trials of non-infectious uveitis. Thinning of choroid and decrease of vessel diameter are observed in patients with chronic NIU compared to controls.

Longitudinal spectral domain optical coherence tomography changes in eyes with intraocular lymphoma.

BACKGROUND: Cases of patients with primary intraocular lymphoma (PIOL) were retrospectively analyzed to describe the longitudinal intra-retinal morphological changes in PIOL as visualized on images obtained by spectral domain optical coherence tomography (SD-OCT). RESULTS: In a retrospective case series, Heidelberg Spectralis SD-OCT images obtained in the longitudinal evaluation of patients with biopsy-proven PIOL were analyzed and assessed. The images were graded for the presence of macular edema (ME), pigment epithelial detachment (PED), subretinal fluid (SRF), and hyperreflective signals. SD-OCT scans of five eyes from five patients were assessed. Patients showed signs of inflammation, such as ME and SRF, which were resolved with treatments in some cases. Hyperreflective signals were found in all eyes in the form of nodules or bands across the retina, with the highest frequency of appearance in the ganglion cell layer, inner plexiform layer, photoreceptor layer, and retinal pigment epithelium; such signals increased with the progression of PIOL. CONCLUSION: SD-OCT may be employed to monitor the progression of PIOL. Hyperreflective signals on OCT may correspond with increase in disease activities, along with other findings such as ME, PED, and SRF.

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

BACKGROUND: The 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. RESULTS: Seventy-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. CONCLUSIONS: Ultra-wide-field fluorescein imaging and angiography can provide additional information that may be important and relevant in the management of retinal vasculitis.

Ocular tolerability and efficacy of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis: primary 6-month results of the SAVE Study.

BACKGROUND: The purpose of this study is to evaluate the ocular tolerability and efficacy of sirolimus administered as subconjunctival or intravitreal injections in patients with non-infectious uveitis. Sirolimus as a Therapeutic Approach for Uveitis (SAVE) is a prospective, randomized, open-label, interventional study. Thirty patients were enrolled and randomized in 1:1 ratio to receive either intravitreal injections of 352 µg sirolimus or subconjunctival injections of 1,320 µg at days 0, 60, and 120, with primary endpoint at month 6. RESULTS: At month 6, all subjects with active uveitis at baseline showed reduction in vitreous haze of one or more steps. Forty percent of subjects showed reduction of two steps or more of vitreous haze (four in each group), and 60% showed a reduction of one-step vitreous haze (seven in group 1 and five in group 2). Changes in the inflammatory indices were statistically significant (p < 0.05) in both study groups. Thirty percent of patients gained one or more lines of visual acuity, 20% lost one or more lines, and 50% maintained the same visual acuity. There were no statistically significant differences between the two study groups at month 6. No serious adverse events were found to be related to the study drug. CONCLUSION: Local administration of sirolimus, either intravitreally or subconjunctivally, appears to be safe and tolerable. No drug-related systemic adverse events or serious adverse events were noted. Sirolimus delivered as either an intravitreal or subconjunctival injection has demonstrated bioactivity as an immunomodulatory and corticosteroid-sparing agent in reducing vitreous haze and cells, improving visual acuity, and in decreasing the need for systemic corticosteroids.

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.

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.

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.