Relationship between macular perfusion and lesion distribution in diabetic retinopathy.

BACKGROUND/OBJECTIVES: To assess the relationship between macular vessel density metrics and foveal avascular zone (FAZ) characteristics on optical coherence tomography angiography (OCTA) and lesion distribution in eyes with diabetic retinopathy (DR). SUBJECTS/METHODS: Patients with DR who underwent both Optos ultrawidefield (UWF) pseudocolor imaging and macular OCTA (Cirrus Angioplex, 6 × 6 mm) were included in this cross-sectional observational study. The distribution of DR lesions was assessed by comparing each of the peripheral ETDRS extended fields (3-7) against their corresponding ETDRS field, hence eyes were defined as either having predominantly peripheral lesions (PPL) or predominantly central lesions (PCL). En face OCTA images from the superficial and deep capillary plexuses (SCP and DCP) were then analysed using Image J software. Perfusion density (PD), vessel length density (VLD), and fractal dimensions (FD) were calculated following binarization and skeletonization of the images. RESULTS: Out of 344 eyes, 116 (33.72%) eyes had PPL and 228 (66.28%) eyes had PCL. For all DRSS levels, VLD, PD, and FD were not significantly different between eyes with PPL and PCL. The FAZ in eyes with PPL, however, was found to be more circular in shape compared to eyes with PCL (p = 0.037). CONCLUSION: Although the presence of PPL has been associated with a higher risk for diabetic retinopathy progression, the macular perfusion is similar in eyes with PPL and PCL. The FAZ is more circular in eyes with PPL, but the clinical relevance of this difference remains to be defined.

Alterations of the Ganglion Cell Complex in Age-Related Macular Degeneration: An Amish Eye Study Analysis.

PURPOSE: To compare the ganglion cell complex (GCC) thickness in eyes with age-related macular degeneration (AMD) vs healthy controls in an elderly Amish population. DESIGN: Prospective cross-sectional study. METHODS: This is a post hoc analysis of the family-based prospective study of Amish subjects. Study subjects underwent imaging with the Cirrus HD-OCT (Carl Zeiss Meditec Inc) using a macular cube protocol of 512 × 128 scans (128 horizontal B-scans, each comprising 512 A-scans) over a 6 mm × 6 mm region centered on the fovea. The ganglion cell analysis algorithm calculated the GCC thickness by segmenting the outer boundaries of the retinal nerve fiber layer (RNFL) and inner plexiform layer (IPL) in all B-scans of the volume, with the region between these boundaries representing the combined thickness of the ganglion cell layer (GCL) and the IPL. A number of parameters were used to evaluate the GCC thickness: the average GCC thickness, minimum (lowest GCC thickness at a single meridian crossing the elliptical annulus), and sectoral (within each of 6 sectoral areas: superior, superotemporal, superonasal, inferior, inferonasal, and inferotemporal). The stage of AMD was graded on color fundus photographs in accordance with the Beckman Initiative for Macular Research classification system. RESULTS: Of 1339 subjects enrolled in the Amish eye study, a total of 1294 eyes of 1294 subjects had all required imaging studies of sufficient quality and were included in the final analysis. Of these, 798 (62%) were female. Following age adjustment, the average GCC thickness was significantly (P < .001) thinner in AMD subjects (73.71 ± SD; 13.77 µm) compared to normals (77.97 ± 10.42 µm). An independent t test showed that the early AMD (75.03 ± 12.45 µm) and late AMD (61.64 ± 21.18 µm) groups (among which eyes with geographic atrophy [GA] had the lowest thickness, of 58.10 ± 20.27 µm) had a statistically significant lower GCC thickness compared to eyes without AMD. There was no significant differences in average GCC thickness between early AMD and intermediate AMD (76.36 ± 9.25 µm) eyes. CONCLUSIONS: The GCC thickness in AMD eyes is reduced compared to normal eyes; however, the relationship is complex, with the greatest reduction in late AMD eyes (particularly eyes with GA) but no difference between early and intermediate AMD eyes.

Impact of slab selection on the relationship between choriocapillaris flow deficits and enlargement rate of geographic atrophy.

OBJECTIVE: To evaluate the effect of changing slab position on the correlation between choriocapillaris (CC) flow deficits (FD) in eyes with geographic atrophy (GA) and yearly enlargement rate (yER) of GA. METHODS: OCT and OCTA images obtained on Cirrus HD-OCT device were collected from patients with GA. Each patient underwent OCTA scan at baseline and two OCT scans, one at baseline and one after at least 12 months. GA was delineated on en-face fundus image to calculate yER. OCTA images were generated from three 10 µm thick slabs 11, 21 and 31 µm posterior to RPE-fit line. 100 µm-wide concentric rings were generated around GA to calculate FD% in each ring which was correlated with yER. RESULTS: For the 11-21 µm slab, FD% was not significantly correlated with yER for any of the rings (p > 0.05). For the 21-31 and 31-41 µm slab, FD% of rings located in the 600 µm region around GA was significantly correlated with yER (p < 0.05). However, in all slab locations, there was no significant correlation between yER and CC FD% of rings located beyond the 600 µm region (p > 0.05). CONCLUSIONS: Slab selection for quantification of CC FD% may have a significant impact on quantitative results in eyes with GA.

OCT outcomes as biomarkers for disease status, visual function, and prognosis in diabetic macular edema.

OBJECTIVE: To evaluate disorganization of retinal inner layers (DRIL), as detected on spectral-domain optical coherence tomography (OCT) images, as a biomarker for diabetic macular edema (DME) activity, visual function, and prognosis in eyes with DME. DESIGN: Longitudinal prospective. METHODS: Post hoc correlation analyses were performed on data from a phase 2 clinical trial. Seventy-one eyes of 71 patients with treatment-naive DME received either suprachoroidally administered CLS-TA (proprietary formulation of a triamcinolone acetonide injectable suspension) combined with intravitreal aflibercept or intravitreal aflibercept with a sham suprachoroidal injection procedure. DRIL area, maximum horizontal extent of DRIL, ellipsoid zone (EZ) integrity, and the presence and location of subretinal (SRF) and intraretinal fluid (IRF) were evaluated at baseline and week 24 by certified reading centre graders. RESULTS: At baseline, the area and maximum horizontal extent of DRIL were negatively correlated with best-corrected visual acuity (BCVA; r = -0.25, p = 0.05 and r = -0.32, p =0.01, respectively). Mean baseline BCVA progressively worsened with each ordinal drop in EZ integrity, improved with the presence of SRF, and was invariant to the presence of IRF. DRIL area and maximum extent were significantly decreased at week 24 (-3.0 mm2 [p < 0.001] and -775.8 mm [p < 0.001], respectively. At week 24, decreases in the area and maximum horizontal extent of DRIL were positively correlated with increases in BCVA (r = -0.40, p = 0.003 and r = -0.30, p = 0.04). Improvements in BCVA at week 24 were no different between patients showing improvement in EZ, SRF, or IRF and those showing no improvement or worsening from baseline. CONCLUSIONS: DRIL area and DRIL maximum horizontal extent were demonstrated to be novel biomarkers for macular edema status, visual function, and prognosis in eyes with treatment-naive DME.

Age-Related Alterations of the Macular Choroid in Healthy Eyes Assessed by Swept-Source Optical Coherence Tomography Angiography.

OBJECTIVE: To analyze age-related changes in the choroid in healthy eyes using swept-source optical coherence tomography angiography (SS-OCTA). PATIENTS AND METHODS: This was a cross-sectional, prospective, observational study enrolling 222 eyes of 116 healthy participants. SS-OCTA images were captured using the PLEX Elite 9000 (Carl Zeiss Meditec) with a 6 x 6 mm pattern centered on the fovea. Subfoveal choroidal thickness (CT) and choroidal volume (CV) were generated automatically through manufacturer tools available in the Advanced Retinal Imaging (ARI) hub network. Choroidal vascularity index (CVI) and choriocapillaris flow deficits (CCFD) were computed using ImageJ. RESULTS: CV was found to be significantly higher in women than men. Overall, there was a significant positive correlation between CVI and CCFD, and a significant negative correlation between CT and CV with age. The relationship, however, was more complex, as a decade-wise analysis showed that CT and CV increased until the second decade, followed by a decrease until the sixth decade, and then an increase again in the seventh and eighth decades. CVI was highest in the seventh decade. In contrast, CCFD increased consistently with age and in all the Early Treatment of Diabetic Retinopathy Study (ETDRS) rings. CONCLUSION: The choroidal blood flow and its thickness reduces as the age advances. While the choroidal flow deficits show a consistent increase with age and the distance from the foveal center, the relationship of other parameters with age is more complex. Having a normative database from healthy subjects is imperative for understanding the changes taking place in diseased states. Choroidal parameters can show significant variations with age. These differences are not uniform or consistent with age, highlighting the importance of a normative reference database to assess the significance of choroidal alterations associated with disease. [Ophthalmic Surg Lasers Imaging Retina 2023;54:526-534.].

Fractal analysis of the macular region in healthy eyes using swept-source optical coherence tomography angiography.

PURPOSE: This cross-sectional observational study evaluated the relationship between retinal vascular fractal dimension (FD) and age, as well as other vascular parameters in healthy eyes using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: The study cohort consisted of 222 eyes of 116 healthy participants with no ocular or systemic disease. SS-OCTA images were captured and analyzed using the Plex Elite 9000 and software tools available in the advanced retinal imaging (ARI) network hub. The retinal vascular layers were defined by the instrument's automatic retinal layer segmentation. The fractal analysis was performed on the superficial capillary plexus (SCP), deep capillary plexus (DCP), and the whole retina. Grayscale OCTA images were standardized and binarized using ImageJ and fractal box-counting analyses were performed using Fractalyse software. Pearson's correlation was used to analyze the correlation between FD and retinal vascular parameters. RESULTS: The results showed that FD values were significantly higher in the 6 mm ring and the whole 6 × 6 scan region when compared to the 1 mm ETDRS central subfield. The correlation between age and FD was weak with a significant positive correlation between age and FD of the SCP in the 6 mm ring and between age and FD of the DCP in the 1 mm ring. Overall, differences in FD values in these healthy eyes were extremely small regardless of age or macular location. CONCLUSION: FD values in normal eyes show little variation with age and are relatively stable across the macula. This suggests that FD values may not need adjustment for age or location when evaluated in the context of retinal disease.

Association of anthropometric parameters as a risk factor for development of diabetic retinopathy in patients with diabetes mellitus.

OBJECTIVE: To study the relationship of body fat distribution in patients with diabetes mellitus (DM), and its long-term complications like diabetic retinopathy (DR), in Indian population. METHODS: This was a prospective, cross-sectional observational study involving 1773 subjects diagnosed with DM and 1778 age and gender-matched individuals. The patients with DM were assessed for the presence and severity of DR. Severe non-proliferative DR and proliferative DR were categorised as sight threatening DR (STDR). Anthropometric parameters, i.e., neck circumference (NC); mid-upper arm circumference (MAC); waist circumference (WC); hip circumference (HC); mid-thigh circumference (MTC) and body mass index (BMI) were measured using standardised technique. RESULTS: The mean age was 59.33 ± 9.32 for DM group, and 66.03 ± 11.04 for non-DM group. DM group showed significantly greater NC, WC, and MTC and significantly reduced MAC and weight. HC and BMI were comparable between the groups. There was a significant positive correlation of MAC and WC (with any level of DR) and MAC, WC, and weight (for STDR); and a significant negative correlation of HC and MTC (with any level of DR) and NC, HC, MTC, and BMI (for STDR). Multiple logistic regression analysis confirmed that WC was the single most important predictor for any level of DR and STDR. CONCLUSIONS: Association of body fat distribution with DM and DR appears multifactorial. However, central obesity signified by waist circumference appears to be the significant risk related to the development of DR and STDR in Indian population.

Choriocapillaris flow deficits in polypoidal choroidal vasculopathy using swept source optical coherence tomography angiography.

Purpose: To evaluate the choriocapillaris flow deficits (CCFD) on swept-source optical coherence tomography angiography (SS-OCTA) in eyes with unilateral polypoidal choroidal vasculopathy (PCV), fellow unaffected eyes, and to compare them with age-matched healthy controls. Methods: This study was a cross-sectional study which included treatment-naïve eyes with unilateral PCV (group 1), fellow unaffected eyes of patients with PCV (group 2), and normal eyes (group 3). Using the SS-OCTA, the Choriocapillaris (CC) slab was segmented from the structural optical coherence tomography (OCT) and the corresponding flow map was multiplied after signal compensation. The resultant image was evaluated for CCFD in equidistant squares measuring 1 × 1 mm, 1.5 × 1.5 mm, 2 × 2 mm, 2.5 × 2.5 mm, 3 × 3 mm, and 6 × 6 mm centered on the fovea. Results: The percentage of flow deficits were significantly increased (one-way ANOVA, P = 0.003 and P = 0.049) in the eyes with PCV as compared to the fellow eyes, and age-matched healthy controls. In the multiple pairwise comparison using post hoc Bonferroni, CCFD of 1 mm in group 1 and 2 (P = 0.019), group 1 and 3 (P = 0.003), and CCFD of 1.5 mm in group 1 and 3 (P = 0.044) were statistically significant. Correlation analysis showed no significant correlation between CCFD, age, Best corrected visual acuity (BCVA), foveal thickness (FT), and subfoveal choroidal thickness (SFCT) in our study. Linear regression analysis showed that the CCFD was negatively correlated with the distance from the foveal center in group 1 (ß = -0.613, P = 0.046). Conclusion: Eyes with PCV demonstrated a significant flow impairment in the choriocapillaris layer as compared to the fellow unaffected eyes and age-matched healthy eyes.

Age-related assessment of foveal avascular zone and surrounding capillary networks with swept source optical coherence tomography angiography in healthy eyes.

AIM: To assess the macular capillary networks and foveal avascular zone (FAZ) with swept-source optical coherence tomography angiography in healthy eyes. METHODS: This cross-sectional, prospective, observational study enrolled 222 eyes of 116 healthy participants with no ocular or systemic disease. SS-OCTA images were captured using the PLEX Elite 9000 (Carl Zeiss Meditec Inc., Dublin, CA, USA) with a 6 × 6 mm pattern centered on the foveal center. Vessel length density (VLD), perfusion density (PD), and FAZ parameters were analyzed using the manufacturer's automated software. RESULTS: A significant negative correlation was observed between age and average VLD in the superficial plexus, and average PD in both the superficial plexus and the whole retina. A significant positive correlation between age and foveal avascular zone perimeter and area was also noted. Age-wise comparisons showed a trend for an increase in VLD and PD until 40 years of age, with a subsequent decrease in the older age in the macular region. The central subfield showed a decrease in the vessel density measurements in the 21-40 age group. FAZ area and perimeter were the mirror inverse of the central subfield vessel density measurements with a numerically greater area and perimeter in the 21-40 age group compared to the 0-20 and 41-60 age groups. FAZ circularity was significantly reduced after 40 years of age. CONCLUSION: Age-related changes in the vessel density and FAZ parameters in the healthy macula are complex and vary with the macular location. These results carry significance when interpreting the data from diseased eyes.

Corneal Topographic versus Manifest Refractive Astigmatism in Patients with Keratoconus: A Retrospective Cross-Sectional Study.

Purpose: To compare the subjective manifest astigmatism to the corneal topographic astigmatism in patients with keratoconus. Methods: This retrospective study included data of 230 keratoconic eyes of 115 patients. Topographic corneal astigmatism (TA), which was measured by pentacam, was compared and correlated to manifest refractive cylinder (MRC) in terms of power, axis, vector components, and mean vector. The difference between TA and MRC was correlated to the maximum keratometric reading (Kmax) and the thinnest pachymetry location (TL), as indicators of keratoconus severity. Results: There was a significant positive correlation between MRC power and TA power (p < 0.001; r = 0.58). TA power was significantly higher than MRC power (p < 0.001). A significant correlation was present between the axis of TA and MRC (r = 0.73; p < 0.001) with the axis of the MRC tending to be more vertical (more against the rule) than the axis of TA. The vector difference between TA and MRC is correlated to the Kmax (p < 0.001; r = 0.62) and TL (p < 0.001; r = 0.3). Conclusions: A significant difference is present between TA and MRC in keratoconic eyes, the power of MRC tends to be less and the axis tends to be more vertical than those of TA; this difference increases as keratoconus becomes more advanced.

Evaluation of Urgent Retinal Practice and Safety Measures for Physicians and Patients During COVID-19 Pandemic.

Purpose: To assess the impact of the COVID-19 pandemic on urgent retina practice and factors influencing adherence of physicians and patients to safety measures. Methods: In this clinical audit, urgent or emergent vitreoretinal surgical disorders that presented to our hospital during the period of 15th March-15th May 2020 were compared with the period just before the pandemic declaration (15th December 2019-15th February 2020). Additionally, two questionnaires assessing the adherence to safety measures were circulated to the medical personnel and a sample of patients. The collected data were analyzed, and accordingly, recommendations were proposed to the hospital administration and specific corrective measures were applied. The outcome of applying these corrective measures was assessed in the re-audit cycle during the period of 15th June-15th August 2020. Results: There was a significant decrease in the number of urgent or emergent vitreoretinal surgical disorders that presented to our hospital during the pandemic (161 versus 302 cases in a similar period before the pandemic; p = 0.022). Just with the pandemic recession, there was a significant increase in the number of urgent cases (391 versus 161 cases during the pandemic; p = 0.006), also there was an increased number of complex cases. Residents and fellows were less compliant than attending physicians in adherence to safety measures. Conclusion: Delayed presentation of urgent retinal cases during the pandemic highlights the importance of public awareness of urgent conditions that need immediate medical or surgical care. Attention to young physicians during the pandemic is crucial as they are less adherent to safety measures due to work overload.

Safety and efficacy of pterygium extended removal followed by extended conjunctival transplant for recurrent pterygia.

PURPOSE: To study the safety and efficacy of pterygium extended removal followed by extended conjunctival transplant for recurrent pterygia. METHODS: Thirty-three eyes of 33 subjects with recurrent pterygia were enrolled in this prospective case series study. Pterygium extended removal followed by extended conjunctival transplantation was performed in all subjects. One surgeon (WA) performed all surgeries. All subjects completed follow-up for at least 12 months and were evaluated for recurrence and complications. RESULTS: The mean age of the participants was 41.2 ± 10.3 years (range 22-60), 7 females (21.2%). The mean duration of follow-up was 25.64 ± 9.24 months (range 12-43). Corrected distance visual acuity (decimal notation) improved from 0.69 ± 0.22 (range 0.2-1.0) at presentation to a 1-year postoperative value of 0.83 ± 0.2 (range 0.3-1.0). No recurrence was reported in all subjects throughout the follow-up period. Transient graft swelling was recorded in 14 cases (42.4%) and resolved in all cases by the first week. All patients developed variable degrees of transient postoperative diplopia that resolved completely by the first 6 weeks. Donor site granuloma developed in 4 cases (12.1%). Spontaneous resolution was observed in 3 cases, while in one case, surgical excision was performed 2 months after the procedure. CONCLUSIONS: In this study of eyes with recurrent pterygia, pterygium extended removal followed by extended conjunctival transplant was found safe and effective with no recurrence and minimal postoperative complications.

Association of severity of diabetic retinopathy with corneal endothelial and thickness changes in patients with diabetes mellitus.

OBJECTIVE: To analyse the central corneal thickness, endothelial cell density and morphology in patients with diabetes mellitus (DM). METHODS: We analysed corneal endothelium, i.e. central corneal thickness (CCT), endothelial cell density (ECD), coefficient of variation in cell size (CV), and hexagonality (Hex) with specular microscopy in patients with type 2 DM and compared with age-matched controls. The influence of diabetic retinopathy (DR) severity, duration of DM, and level of glycosylated haemoglobin (HbA1c) was also analysed. RESULTS: The study cohort included 592 eyes of 592 diabetic patients and 596 eyes of 596 control subjects. A significant difference was found in CCT (522.1 ± 36.6 µm in DM, 514.9 ± 37.1 µm in controls; P = 0.001), ECD (2484.5 ± 299.5 cells/mm2 in DM, 2555.9 ± 258.2 cells/mm2 in controls; P = 0.017), CV (40.3 ± 6.1 in DM, 37.2 ± 6.1 in controls; P < 0.001) and Hex (39.9 ± 5.2 in DM, 44.6 ± 6.0 in controls; P < 0.001). The longer duration of DM ( > 10 years) and poor glycaemic control (HbA1c > 7.5%) were associated with similar results. A significantly reduced ECD (P < 0.001) and Hex (P = 0.001) and higher CV (P = 0.007) and CCT (P = 0.01) was noted when assessed against various stages of DR. Multivariate analysis showed that increasing age was significantly associated with lower ECD (P < 0.001), Hex (P < 0.001), and CCT (P = 0.004); and a higher CV (P < 0.001). CONCLUSIONS: DM has deleterious effects on corneal endothelium and thickness. The presence of DR may further warrant a thorough corneal evaluation, especially when planning intraocular surgery.

Natural history of incomplete retinal pigment epithelial and outer retinal atrophy in age-related macular degeneration.

OBJECTIVE: To assess the time course and risk factors for conversion of incomplete retinal pigment epithelium and outer retina atrophy (iRORA) to complete retinal pigment epithelium and outer retina atrophy (cRORA) in eyes with non-neovascular intermediate age-related macular degeneration (iAMD), using optical coherence tomography (OCT) analysis. DESIGN: Retrospective survival study. PARTICIPANTS: Tracked structural Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) volume datasets from 2 retinal specialists at the University of California-Los Angeles were retrospectively screened to identify consecutive participants with non-neovascular iAMD without signs of atrophy or macular neovascularization in either eye at baseline. METHODS: In the first stage of selection, 321 consecutive iAMD eyes were screened for onset of iRORA. Eyes that developed iRORA within the first 24 months were followed for an additional 24 months to assess the rate of conversion to cRORA. A Kaplan-Meier survival curve was formulated to illustrate the conversion from iRORA to cRORA. RESULTS: Among 321 baseline participants with iAMD, 87 incident iRORA lesions (50 eyes, 42 participants) were included in the conversion analysis. Eighty-one iRORA lesions (93.1%) converted to cRORA within 24 months (median 14 months). Multivariate binary logistic regression analysis indicated that intraretinal hyperreflective foci and extrafoveal iRORA location at baseline were associated with a faster rate of progression to cRORA (model R2 = 0.816, p < 0.05). CONCLUSIONS: The majority of incident iRORA lesions progress to cRORA within a 24-month period. These findings may be of value in the design of early intervention trials for risk stratification and prognostication but need to be validated with a prospective analysis.

Intravitreal injections of anti-VEGF agents during COVID-19 pandemic: clinical audit from Tanta University Hospital.

BACKGROUND: The aims of this study were to provide real-life data about the effect of COVID-19 pandemic on the practice of anti-VEGF injections and to evaluate the safety of the modifications in the injection protocol imposed during the ongoing pandemic on the anatomical and functional outcome of patients. METHODS: All patients attending Tanta University hospital for receiving intravitreal anti-VEGF injections were screened. Patients who were previously deferred according to a modified protocol implemented in the hospital in response to the pandemic or who demonstrated deviation from it were included for further analysis. RESULTS: During the audit period, 83 patients attending for anti-VEGF injections were screened, of whom 40 met the abovementioned criteria and were included for analysis. In the deferred subgroup (11 eyes), predeferral mean values of logMAR best corrected visual acuity (BCVA) and central retinal subfield thickness (CST) were 1 ± 0.23 and 444.57 ± 200.1 µm, respectively. There was no significant change when the patients returned for their deferred injections, with the mean BCVA and CST values being 0.8 ± 0.22 and 413.71 ± 237.7 µm, respectively (p = 0.27 and p = 0.12). Moreover, 29 patients encountered a disturbed injection schedule, particularly skipping their injection appointments due to infection fear as found in 18 patients. CONCLUSION: The COVID-19 pandemic has imposed pressing challenges in maintaining essential health care while ensuring the prevention of spread of infection. Although the modified injection protocol confirmed to be safe for patients, the pandemic caused deflection from the optimum practice in the form of successive skipping of appointments and delays in the processing of patient injection schedules.

Effect of Aflibercept on Diabetic Retinopathy Severity and Visual Function in the RECOVERY Study for Proliferative Diabetic Retinopathy.

PURPOSE: To evaluate the effect of intravitreal aflibercept on diabetic retinopathy (DR) severity and visual function in patients with proliferative DR (PDR) without diabetic macular edema (DME). DESIGN: Prospective, longitudinal, multicenter clinical trial. PARTICIPANTS: Forty eyes of 40 patients with PDR and no DME were enrolled in this study. Patients were randomized into monthly and quarterly 2-mg aflibercept injection cohorts and were treated over a period of 12 months. METHODS: All patients underwent ultra-widefield fundus imaging including pseudocolor and fluorescein angiography using an Optos 200Tx device. MAIN OUTCOME MEASURES: Severity of DR at baseline, month 6, and month 12 was evaluated using the DR severity scale (DRSS). The DRSS scores were correlated with the 25-item Visual Function Questionnaire (VFQ-25) and 39-item Visual Function Questionnaire (VFQ-39) scores at baseline and month 12. RESULTS: Mean age of the patients was 48.2 years (range, 25-75 years), mean duration of diabetes mellitus was 16.1 years (range, 2-36 years), and median glycated hemoglobin level was 8.8% (IQR, 7.4%-10%). Both monthly and quarterly groups demonstrated a statistically significant regression in DRSS from baseline to month 12 (P < 0.001). The monthly group demonstrated a statistically significant greater regression of DRSS score at the month 6 visit compared with the quarterly group (P = 0.019). However, the difference between the two groups became statistically insignificant at month 12 visit (P = 0.309). Also no difference was found in mean VFQ-25 and VFQ-39 composite scores between the monthly and quarterly groups at month 12 (P = 0.947 and P = 0.921, respectively). The improvement in mean VFQ-25 and VFQ-39 composite scores at month 12 was correlated significantly with improvement in DRSS score (r = 0.384 and P = 0.039, and r = 0.361 and P = 0.046, respectively). CONCLUSIONS: In this study of eyes with PDR without DME, both monthly and quarterly aflibercept injection groups showed significant improvement in DR severity at month 12 compared with baseline. The improvement in DRSS score was associated with an improvement in VFQ-25 and VFQ-39 composite score.

Peripheral extent of the choroidal circulation by ultra-widefield indocyanine green angiography in healthy eyes.

AIM: To analyse the peripheral extent of choroidal circulation using ultra-widefield (UWF) indocyanine green angiography (ICGA) in healthy eyes. METHODS: UWF ICGA images of 55 eyes of 36 healthy subjects were captured using the Optos California (Optos, Dunfermline, United Kingdom) in this prospective observational study. Images were analysed to locate the peripheral extent of the visible choroidal circulation, and the boundary was marked in ImageJ (v1.52). Each pixel annotated as the border of the choroidal circulation was projected individually to its anatomically correct location on the three-dimensional model eye, and spherical trigonometry was applied (using the Optos software) to calculate its respective radial distance from the centre of the optic disc in metric units (corrected by stereographic projection) for each quadrant. RESULTS: The mean area of the peripheral extent was estimated to be 893.2 mm2 (95% CI: 844.2 to 942.3 mm2). The mean distance (range) of this boundary from optic nerve centre was 18.22 mm (95% CI: 14.0 to 23.14 mm). Multiple regression analysis with age, gender, axial length or ethnicity showed no relationship. There was excellent inter-grader reproducibility, with intraclass correlation coefficients of 0.95 (95% CI: 0.80 to 0.99, p<0.001) for distance and 0.99 (95% CI: 0.988 to 0.999, p<0.001) for area measurements. CONCLUSIONS: The peripheral choroidal boundary may be defined using UWF ICGA. Knowledge of the normal extent and its variability is essential to understand the impact of disease on the choroidal vasculature.

CHORIOCAPILLARIS FLOW DEFICITS AS A RISK FACTOR FOR PROGRESSION OF AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the association between choriocapillaris (CC) flow deficits and structural optical coherence tomography biomarkers and the progression of intermediate age-related macular degeneration (iAMD) to complete retinal pigment epithelial and outer retinal atrophy. METHODS: Retrospective analysis of consecutive patients with iAMD with a minimum follow-up of 12 months. Odds ratios of intraretinal hyperreflective foci, hyporeflective drusen cores, subretinal drusenoid deposits, the presence of drusen volume ≥0.03 mm3 within a central 3-mm circle, fellow eye with late stage of AMD, and CC flow deficits at baseline and months of follow-up were estimated from logistic regression. RESULTS: A total of 112 eyes with iAMD were included. Eyes that progressed were significantly more likely to show intraretinal hyperreflective foci, hyporeflective drusen cores, and drusen volume ≥0.03 mm3. The CC flow deficit was also significantly greater in eyes that developed complete retinal pigment epithelial and outer retinal atrophy. Intraretinal hyperreflective foci, hyporeflective drusen cores, drusen volume ≥0.03 mm3, and higher CC flow deficits were significantly and independently associated with the development of complete retinal pigment epithelial and outer retinal atrophy. CONCLUSION: The CC flow deficit was significantly greater in iAMD eyes that progressed to complete retinal pigment epithelial and outer retinal atrophy and remained an independent risk factor when structural optical coherence tomography biomarkers were considered. CC flow deficits may be useful for enhancing risk stratification and prognostication of patients with iAMD.

Scotopic microperimetric sensitivity and inner choroid flow deficits as predictors of progression to nascent geographic atrophy.

BACKGROUND/AIMS: To assess the role of microperimetric retinal sensitivity (MPRS) and inner choroid flow deficits (IC FD) in predicting the development of incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) in intermediate AMD (i-AMD). METHODS: Thirty eyes with i-AMD evaluated at the Doheny-UCLA Eye Centres were enrolled in this prospective IRB-approved study. Subjects underwent several diagnostic tests: (a) 6×6 mm swept-source optical coherence tomography angiography (SS-OCTA) with the IC slab used to quantify the FDs, (b) 20°×20° spectral-domain optical coherence tomography (SD-OCT) to monitor progression to iRORA and (c) scotopic MPRS within an area of 18° centred on the fovea. All subjects were followed-up for 24 months. The baseline IC FD and MPRS were correlated with the development of iRORA. At 24-month follow-up, the stage of AMD was re-assessed and the eyes were divided into two sub-groups based on the development of iRORA. RESULTS: Twenty-eight eyes completed the 2-year follow-up. At baseline, the mean MPRS was 13.40±4.66 dB and the mean IC FD was 27.55±8.67%. The morpho-functional regression showed a significant correlation between baseline MPRS and IC FD and the development of iRORA within 24 months (R2=0.744, p<0.05). A Kaplan-Meier survival curve was fit to determine the cumulative incidence of iRORA over the 24 months. CONCLUSIONS: A lower MPRS and greater IC FD at baseline were predictors of progression to iRORA in eyes with i-AMD. These parameters may be useful biomarkers for risk stratification and prognostication.