Association of macular and choroidal perfusion with long-term visual outcomes after macula-off rhegmatogenous retinal detachment.

BACKGROUND/AIMS: To examine the relationship between macular perfusion, as assessed using optical coherence tomography angiography (OCTA), and long-term visual outcome after surgical repair of macula-off rhegmatogenous retinal detachment (RRD). METHODS: A prospective study of 29 patients who had undergone successful surgical repair of macula-off RRD. OCTA imaging was performed at month 3 and repeated at months 6 and 12 after surgery. Associations between OCTA parameters including, foveal avascular zone (FAZ) area, vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), choriocapillaris flow deficit features and logMAR best-corrected visual acuity (VA) were assessed using a random intercept hybrid linear mixed model. RESULTS: Over the 1-year follow-up, VA improved (0.025 logMAR/ month, 95% CI 0.015 to 0.035) and FAZ area decreased (-0.020 mm2/month, 95% CI -0.032 to -0.007). Better VA after surgery was significantly associated with denser superficial VD (ß=0.079, 95% CI 0.026 to 0.131), lower number of choriocapillaris flow deficits (ß=-0.087, 95% CI -0.154 to -0.021) and larger average size of choriocapillaris flow deficits (ß=0.085, 95% CI 0.022 to 0.147), after adjusting for baseline VA, types of surgery and other factors. CONCLUSIONS: OCTA measures of vascular perfusion in the macula may provide new pathophysiological insights and prognostic information related to macula-off RRD.

25-years Trends and Risk factors related to Surgical Outcomes of Giant Retinal Tear-Rhegmatogenous Retinal Detachments.

To describe the 25-year surgical trends, long-term outcomes and risk factors affecting the outcomes of giant retinal tear-related rhegmatogenous retinal detachments (GRT-RRD). Patients' demographics, pre-operative characteristics, risk factors, operative procedures and post-operative outcomes were collected and divided into three groups - Group A: 1991 to 2015 (overall); Group B: 1991 to 2005, and Group C: 2006 to 2015. Functional and anatomical successes were monitored over a 5-year period. Multivariate logistic regression analysis was performed to identify the risk factors related to functional and anatomical success.127 eyes of 127 patients were included in the study. At 5th year, 69.4% patients had visual acuity (VA) < logMAR 1.0 with 87.5% primary anatomical success rate. While the functional outcome remained the same between group B and C, there was an increase in the anatomical success from 89.7% to 100%, albeit not statistically significant. Patients with worse presenting VA, 150 degrees or more of giant retina tear, macula-detached status and presence of PVR were associated with VA of> logMAR 1.0 (all p < 0.05). The types of surgery (TPPV vs combined SB/TPPV), number of breaks, lens extraction and additional cryotherapy were not associated with the functional or anatomical success. In conclusion, the GRT-RRD functional and structural outcomes were comparable between 1991-2005 and 2006-2015, albeit a statistically insignificant improvement of anatomical outcome over the past 25 years. Worse presenting VA, 150 degrees or more of giant retinal tear, detached macula and presence of PVR were associated with poorer visual outcome.

Diet and risk of myopia in three-year-old Singapore children: the GUSTO cohort.

BACKGROUND: To investigate the relationship between dietary intakes at six, nine and 12 months and risk of myopia in three-year-old children in a birth cohort. METHODS: Three hundred and seventeen children from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study were included. Dietary intake at six, nine and 12 months of age was ascertained using either 24-hour recalls or three-day food diaries completed by parents. Cycloplegia was achieved with three drops of one per cent cycloplentolate instilled at five minute intervals. Cycloplegic autorefraction and axial length (AL) were measured at three years of age with a table-mounted autorefractor and optical biometer, respectively. Myopia was defined as spherical equivalent (SE) of ≤ -0.50 D. Associations of dietary intake with SE, AL and myopia were examined by single dietary factor models using two multivariable regression models. Model 1 included adjusting for age, gender and total energy intake. Model 2 included additional adjustments for ethnicity, time spent outdoors, maternal education and parental myopia. RESULTS: In the single dietary factor adjusted models, dietary intakes at six, nine and 12 months were not associated with SE, AL and myopia. In model 1, protein, fat and carbohydrate intakes were not associated with SE, AL and myopia at any of the three time points (p > 0.05). In model 2, protein, fat and carbohydrate intakes were not associated with SE, AL and myopia at any of the three time points (p > 0.05). CONCLUSIONS: In this study, there was no evidence that diet at ages six, nine and 12 months was related to SE, AL or myopia at age three years. Further prospective studies with larger sample sizes are needed to understand the influence of diet on eye development in young children.

Retinal Vessel Geometry and the Incidence and Progression of Diabetic Retinopathy.

Purpose: To analyze the associations between retinal vessel geometry and the 1-year incidence and progression of diabetic retinopathy (DR) in a Chinese population. Methods: This was a prospective cohort study of adult subjects with diabetes mellitus. Retinal vascular geometry was quantified from fundus photographs using a semiautomated computer-assisted program. Diabetic retinopathy was graded from retinal photographs at baseline and 1 year. Incident DR and 2-step change in DR were analyzed. Results: In total, 249 subjects were included. Their mean age was 59.9 ± 8.9 years, 74% were male, and the mean glycated hemoglobin A1c (HbA1C) and duration of diabetes were 7.7 ± 1.4% and 14.3 ± 10.6 years, respectively. The distribution of DR severity at baseline was no DR in 35.7%, minimal nonproliferative diabetic retinopathy (NPDR) in 15.3%, mild NPDR in 14.6%, moderate NPDR in 23.1%, severe NPDR in 5.1%, and proliferative DR in 6.1% of eyes. In multivariate analyses adjusting for age, duration of diabetes, sex, smoking status, HbA1c, hypertension, and hyperlipidemia, subjects with higher venular fractal dimensions were more likely to have incident DR (odds ratio [OR] 0.38, [95% confidence interval (CI), 0.15-0.96], P = 0.032, per SD decrease). Lower venular tortuosity was associated with a lower likelihood of DR progression (OR 0.76, [95% CI, 0.59-0.97], P = 0.005, per SD decrease). Lower arteriolar tortuosity was associated with a greater likelihood of DR regression (OR 1.95, [95% CI 1.07-3.56], P = 0.037, per SD decrease). Conclusions: Novel measures of retinal vascular geometry are associated with the incidence and progression of DR at 1 year. These geometric measures are likely to represent early dysfunction in the retinal microvasculature.

Dynamic Responses in Retinal Vessel Caliber With Flicker Light Stimulation and Risk of Diabetic Retinopathy and Its Progression.

Purpose: This study investigated the associations between the responses of retinal vessels to flickering light and the incidence and progression of diabetic retinopathy (DR). Methods: A prospective cohort study of adult subjects with diabetes mellitus. The dynamic vessel analyser (DVA) was used to measure retinal vascular dilatation in response to diffuse illuminance flicker. Diabetic retinopathy was graded from retinal photography at baseline and at 1 year. Incident DR and two-step change in DR were analyzed. Results: There were 276 subjects in total, with a mean age of 59.8 ± 8.9 years. The majority were male (73%) and the mean glycated hemoglobin A1c (HbA1c) level and mean duration of diabetes were 7.7 ± 1.4% and 14.0 ± 10.5 years, respectively. After adjustments for age, sex, smoking, duration of diabetes, HbA1c, hypertension, and hyperlipidemia, the responses of retinal arterioles to flicker stimulation were lower in subjects with incident DR (P = 0.048). Subjects with greater arteriolar dilatory responses were less likely to have DR progression (odds ratio [OR] 1.85, [95% confidence interval [CI] 1.33-2.56], P = 0.012, per SD decrease). Subjects with greater venular dilatory responses were also less likely to have DR progression (OR 1.89, [95% CI 1.35-2.63], P = 0.003, per SD decrease). There were no significant associations between arteriolar or venular dilation response and incident proliferative DR (PDR) and DR regression. Conclusions: Reduced retinal arteriolar and venular dilatory responses to flickering light are associated with risk of DR progression at 1 year in adult patients with diabetes.

Conversion to aflibercept for diabetic macular edema unresponsive to ranibizumab or bevacizumab.

BACKGROUND: The purpose of this study was to determine if eyes with diabetic macular edema (DME) unresponsive to ranibizumab or bevacizumab would benefit from conversion to aflibercept. METHODS: This study was conducted as a retrospective chart review of subjects with DME unresponsive to ranibizumab and/or bevacizumab and subsequently converted to aflibercept. RESULTS: In total, 21 eyes from 19 subjects of mean age 62±15 years were included. The majority of subjects were male (63%). The median number of ranibizumab or bevacizumab injections before switching to aflibercept was six, and the median number of aflibercept injections after switching was three. Median follow-up was 5 months after the switch. Mean central foveal thickness (CFT) was 453.52±143.39 mm immediately prior to the switch. Morphologically, intraretinal cysts were present in all cases. Mean CFT after the first injection decreased significantly to 362.57±92.82 mm (Wilcoxon signed-rank test; P<0.001). At the end of follow-up, the mean CFT was 324.17±98.76 mm (P<0.001). Mean visual acuity was 0.42±0.23 logMAR just prior to the switch, 0.39±0.31 logMAR after one aflibercept injection, and 0.37±0.22 log-MAR at the end of follow-up. The final visual acuity was significantly better than visual acuity before the switch (P=0.04). CONCLUSION: Eyes with DME unresponsive to multiple ranibizumab/bevacizumab injections demonstrate anatomical and visual improvement on conversion to aflibercept.

Comparison of swept source optical coherence tomography and spectral domain optical coherence tomography in polypoidal choroidal vasculopathy.

BACKGROUND: Swept source optical coherence tomography (SS-OCT, Topcon Medical System, Japan) is known to have longer wavelength than spectral domain OCT (SD-OCT, Spectralis, Heidelberg Engineering, Germany), allowing a deeper penetration into retina and choroidal layers. This objective of this study was to compare the visibility of retinal and choroidal features in polypoidal choroidal vasculopathy (PCV) using SS-OCT and SD-OCT. DESIGN: This study employs prospective comparative observational case series in Singapore National Eye Center. PARTICIPANTS: There were 20 eyes (20 patients) with PCV confirmed with indocyanine green angiogram. METHODS: Six pre-specified OCT parameters (presence of polyps, sharp pigment epithelial detachment [PED] peak, notched PED and visibility of full maximum height of PED, inner segment/outer segment [IS/OS] line and choroid-scleral interface [CSI]) were graded using SS-OCT and SD-OCT. MAIN OUTCOME MEASURES: The Kappa statistics between the two imaging modalities were calculated. RESULTS: Both SS-OCT and SD-OCT were able to detect polypoidal lesions in the majority of eyes (90% and 85%, respectively). However, SS-OCT had better detection for CSI and IS/OS lines (CSI: 80% vs 45%, P = 0.05; IS/OS line: 65% vs 45%, P = 0.34). For sharp PED peak, notched PED, ability to visualize the full PED height and retinal pigment epithelial line, both OCT machines were able to detect in ≥80% of the eyes. CONCLUSION: In conclusion, SS-OCT and SD-OCT appeared to be similarly effective at detecting most features associated with PCV. However, SS-OCT is more superior in detecting the CSI.

Relationship of systemic endothelial function and peripheral arterial stiffness with diabetic retinopathy.

BACKGROUND: To investigate possible associations between diabetic retinopathy (DR) and systemic vascular endothelial function and arterial stiffness measured using reactive hyperaemia peripheral arterial tonometry. METHODS: This was a cross-sectional observational clinical study. Subjects with diabetes were recruited and DR was graded from retinal photographs. Systemic endothelial function was measured using reactive hyperaemia peripheral arterial tonometry (EndoPAT) and expressed as the reactive hyperaemia index (RHI). Peripheral arterial stiffness was measured using the same device and expressed as the augmentation index (AI). RESULTS: In total, 164 eyes of 95 Chinese patients were evaluated. The mean age of the subject eyes was 60.1±8.2 years and 76.8% were men. The mean duration of diabetes was 15.5±9.8 years, and the mean HbA1c was 8.1±1.4%. In age-gender-adjusted models, increasing severity of DR was associated with increasing mean RHI (p=0.001) and increasing mean AI (p<0.001). In multivariate models, adjusting additionally for smoking, mean duration of diabetes, HbA1c and hypertension, the associations with RHI and AI persisted (p=0.011 and 0.001, respectively). In analyses of the dichotomous outcomes clinically significant macular oedema (CSME), moderate DR and vision-threatening DR, AI was a significant predictor of CSME and vision-threatening DR. In multivariate-adjusted models, for every SD increase in AI, the odds of having CSME was 1.78 times higher (95% CI 1.05 to 2.99; p=0.029). For every SD increase in AI, the odds of having vision-threatening DR was 1.73 times higher (95% CI 1.17 to 2.56; p=0.003). CONCLUSIONS: Subjects with more severe DR have larger peripheral reactive hyperaemic responses and greater peripheral vascular stiffness. These findings support the link between the microvascular changes of diabetes and macrovascular disease.

Dynamic responses in retinal vessel caliber with flicker light stimulation in eyes with diabetic retinopathy.

PURPOSE: This study investigated the responses of retinal vessels to flickering light in diabetic patients with various stages of diabetic retinopathy (DR). METHODS: This cross-sectional observational study evaluated adult subjects with diabetes mellitus. The Dynamic Vessel Analyzer (DVA) was used to measure retinal vascular dilatation in response to diffuse illuminance flicker. Diabetic retinopathy was graded from retinal photography. RESULTS: There were 279 subjects in total, with a mean age of 59.9 ± 9.2 years. The majority were male (73%) and the mean HbA1c level and mean duration of diabetes were 7.7% ± 1.4% and 13.9 ± 10.4 years, respectively. After adjustments for age, sex, smoking, duration of diabetes, HbA1c, hypertension, and hyperlipidemia, the responses of both retinal arterioles and venules to flicker stimulation decreased continuously with increasing stages of diabetic retinopathy (P = 0.008 and <0.001, respectively). Subjects with reduced arteriolar dilation responses were more likely to have any DR (odds ratio, OR, 1.20, [95% confidence interval (CI), 1.01-1.45], P = 0.045, per SD decrease). Subjects with reduced venular dilation responses were more likely to have any DR, moderate DR, or vision-threatening DR (OR: 1.27 [1.04-1.53], P = 0.02; OR: 1.27 (1.06-1.49), P = 0.007; and OR: 1.51 (1.14-1.50), P = 0.002; per SD decrease, respectively). CONCLUSIONS: The responses of retinal arterioles and venules to flickering light are reduced in subjects with DR, and decrease progressively with more severe stages of DR.

Vitreoretinal complications and vitreoretinal surgery in osteo-odonto-keratoprosthesis surgery.

PURPOSE: To describe the indications for and approaches to vitreoretinal surgery in patients with osteo-odonto-keratoprosthesis (OOKP). DESIGN: Retrospective case series. METHODS: This was a retrospective review of all patients who had undergone OOKP surgery between 2003 and 2012 at our center. OOKP procedures were performed for severe ocular surface disease according to the indications and techniques described in the patient demographics of the Rome-Vienna Protocol. Indications for retinal surgery, surgical outcomes, and intraoperative and postoperative complications were documented. Operative techniques were reviewed from the surgical records, and any subsequent surgeries were also recorded. RESULTS: Thirty-six patients underwent OOKP, and retinal surgery was indicated in 13 (36%). The indications for and approaches to surgery were retinal detachment repair using an Eckardt temporary keratoprosthesis; assessment of retina and optic nerve health prior to OOKP surgery, using either a temporary keratoprosthesis or an endoscope; endoscopic cyclophotocoagulation for intractable glaucoma; endoscopic trimming of a retroprosthetic membrane; or vitrectomy for endophthalmitis with visualization through the OOKP optic using the binocular indirect viewing system. In all cases, retinal surgical aims were achieved with a single procedure. Postoperative vitreous hemorrhage occurred in 16 patients (44%), but all resolved spontaneously. CONCLUSIONS: OOKPs represent the last hope for restoration of vision in severe ocular surface disease, and the retinal surgeon is frequently called upon in the assessment and management of these patients. Temporary keratoprostheses and endoscopic vitrectomies are valuable surgical tools in these challenging cases, improving functional outcomes without compromising OOKP success.

Age-related macular degeneration.

Age-related macular degeneration is a major cause of blindness worldwide. With ageing populations in many countries, more than 20% might have the disorder. Advanced age-related macular degeneration, including neovascular age-related macular degeneration (wet) and geographic atrophy (late dry), is associated with substantial, progressive visual impairment. Major risk factors include cigarette smoking, nutritional factors, cardiovascular diseases, and genetic markers, including genes regulating complement, lipid, angiogenic, and extracellular matrix pathways. Some studies have suggested a declining prevalence of age-related macular degeneration, perhaps due to reduced exposure to modifiable risk factors. Accurate diagnosis combines clinical examination and investigations, including retinal photography, angiography, and optical coherence tomography. Dietary anti-oxidant supplementation slows progression of the disease. Treatment for neovascular age-related macular degeneration incorporates intraocular injections of anti-VEGF agents, occasionally combined with other modalities. Evidence suggests that two commonly used anti-VEGF therapies, ranibizumab and bevacizumab, have similar efficacy, but possible differences in systemic safety are difficult to assess. Future treatments include inhibition of other angiogenic factors, and regenerative and topical therapies.

Lipids and diabetic retinopathy.

INTRODUCTION: Diabetic retinopathy (DR) is a significant cause of visual impairment worldwide. The association between hyperlipidemia or dyslipidemia and DR has been investigated extensively, but a conclusive link remains elusive. This review summarizes the current knowledge regarding lipids and DR. AREAS COVERED: The clinical literature on the associations between the 'traditional' lipid markers and DR will be critically evaluated, along with some of the postulated biological mechanisms underlying the associations. The emergence of several novel 'non-traditional' lipid fractions as possible biomarkers for DR will also be discussed. The review will conclude by evaluating current lipid-lowering therapies in DR and also give an overview of other novel treatments targeting lipid pathways. EXPERT OPINION: Future studies need to address three important issues. First, the role of novel lipid biomarkers needs to be clarified in light of the persistent failure of epidemiological studies to demonstrate a clear association between traditional lipids and DR. Second, the pathways by which lipid-lowering therapies act in preventing the retinal complications of diabetes need to be elucidated. Last, identifying the patient profile that would benefit most from treatment is essential.

Variations in eye volume, surface area, and shape with refractive error in young children by magnetic resonance imaging analysis.

PURPOSE: To determine variations in eye volume, surface area, and shape with refractive error in young children using a three-dimensional magnetic resonance imaging (MRI) model. METHODS: A subset of Singaporean Chinese boys enrolled in the population-based Strabismus, Amblyopia, and Refractive Error in Singapore (STARS) study underwent MRI using a 3-Tesla whole body scanner with a 32-channel head coil. Eye volume and surface area were measured. Eye shape was assessed qualitatively from the three-dimensional models and quantitatively by measurement of the longitudinal axial length (LAL), horizontal width, and vertical height along the cardinal axes. RESULTS: One hundred thirty-four eyes of 67 subjects (mean age, 77.9 ± 3.9 months) were analyzed. The mean spherical equivalent (SE) refraction was 0.65 ± 0.92 D (range, -2.31 to 4.13 D). More myopic SE was associated with larger surface area (-20.59 [-37.09 to -4.10] mm²/D; P = 0.01) but not volume. In age-height adjusted models, more myopic SE was associated with longer LAL (-1.94 [-2.47 to -1.41] mm/D; P < 0.001) and greater width (-1.12 [-1.26 to -0.99] mm/D; P < 0.001) but not height (0.64 [-2.55 to 3.82] mm/D; P = 0.70). In nonmyopic subjects, less hyperopic SE was associated with longer AL (-0.40 [-0.71 to -0.10] mm/D; P = 0.01), width (-0.59 [-0.84 to -0.34] mm/D; P < 0.001), and height (-0.40 [-0.64 to -0.17] mm/D; P = 0.001). In three-dimensional models, myopic eyes conformed to an axial elongation model with a prolate profile in the axial plane, whereas nonmyopic eyes showed global expansion. CONCLUSIONS: Eye surface area increases with myopia in young children. Eye shape is different in myopia, even in its early stages. Axial globe enlargement occurs in myopic eyes leading to a prolate shape, whereas nonmyopic eyes enlarge globally in length, width, and height.

Sequential therapeutic penetrating keratoplasty with cryopreserved and fresh corneal tissue for severe infectious keratitis: a case-control study.

PURPOSE: Sequential therapeutic penetrating keratoplasty (TPK) using a cryopreserved cornea followed soon after by a fresh optical grade cornea for severe infectious keratitis may improve the survival of the optical graft. The aim of this study was to compare the therapeutic efficacy, visual outcomes, and graft survival for sequential TPK against TPK using a fresh optical grade cornea alone. METHODS: This was a retrospective case-control study. Case records were reviewed for clinical and surgical outcomes. RESULTS: Thirty-two eyes of 32 patients were included. Ten eyes underwent sequential TPK (TPK cases), and there were 22 age- and sex-matched controls, which underwent TPK with optical grade tissue alone. The mean interval between the TPK with the frozen cornea and the subsequent optical keratoplasty in the TPK cases was 16.8 ± 12.9 days. Therapeutic success, defined as the eradication of the primary infection, was achieved in all the TPK cases but only in 13 controls (59.1%) (P = 0.06). Graft survival at 1 year was better in the TPK cases than the controls (72.9% vs 53.8%). An improvement in Snellen acuity by at least 2 lines was more likely in the TPK cases than the controls (80% vs 14%; P = 0.001). CONCLUSIONS: Sequential TPK is an effective surgical therapy for active severe infectious keratitis and also helps to conserve valuable optical grade corneal tissue.

Postoperative risk factors influencing corneal graft survival in the Singapore Corneal Transplant Study.

PURPOSE: To determine postoperative risk factors that influence long-term corneal graft survival. DESIGN: Prospective cohort study. METHODS: Nine-hundred one consecutive penetrating keratoplasty procedures for optical, therapeutic, or tectonic indications from the Singapore Corneal Transplant Study. Univariate and multivariate analysis was performed for postoperative risk factors; Cox proportional hazards regression with a time-dependent covariate was used for preoperative, intraoperative, donor, and postoperative risk factors in a combined model. RESULTS: Raised intraocular pressure (20.7%) was the most common complication, followed by rejection (18.2%), whereas glaucoma surgery (7.9%) and repeat grafting (7.3%) were the most common procedures after penetrating keratoplasty. The primary graft failure rate was 1.4%, and late failure was seen in 9.4% of eyes. In the combined regression model, rejection (hazard ratio [HR], 3.4; P = .00), microbial keratitis (HR, 3.6; P = .00), endophthalmitis (HR, 7.7; P = .00), primary disease recurrence (HR, 73.9; P = .00), wound dehiscence (HR, 2.8; P = .02), lid surgery (HR, 2.3; P = .02), glaucoma surgery (HR, 2.46; P = .02), and repeat grafting (HR, 3.2; P = .00) were the significant postoperative failure predictors; the significant preoperative and intraoperative factors identified were female gender, graft size of less than 7 mm and more than 9 mm, primary diagnosis, preoperative inflammation, and preexisting perforation. CONCLUSIONS: Postoperative complications and operative procedures after grafting have an adverse effect on graft survival.

Biological and ultrastructural properties of acelagraft, a freeze-dried γ-irradiated human amniotic membrane.

OBJECTIVES: To compare the biological and ultrastructural properties of a commercially available decellularized and dehydrated human amniotic membrane (DDHAM) product with cryopreserved human amniotic membrane (CHAM) and to demonstrate the feasibility of DDHAM transplant in a case of chronic ocular surface disease. METHODS: Histologic examination, immunohistochemical examination for extracellular matrix molecules and growth factors, transmission and scanning electron microscopy, and atomic force microscopy were performed on both DDHAM and CHAM specimens. A DDHAM transplant was performed in a patient with chronic bullous keratopathy and ocular surface instability. RESULTS: Histologic examination and transmission electron microscopy revealed the disruption of the trilaminar structure of the basement membrane compared with CHAM, and immunohistochemical examination confirmed the loss of collagen IV and VII, laminin, and fibronectin in DDHAM. Lower levels of several growth factors were also seen in DDHAM compared with CHAM. Clinical transplant of DDHAM was, however, successful, with rapid reepithelialization. CONCLUSION: Significant differences in composition and ultrastructure exist between DDHAM and CHAM but do not appear to compromise cell survival in vivo. CLINICAL RELEVANCE: The ease of storage and handling of DDHAM make it potentially valuable in ocular surface surgery, but its biological properties have not been well characterized, and there are also few data on its clinical application.