Proportion of people with diabetic retinopathy and macular oedema varies by ethnicity in a tertiary retinal clinic in Australia: findings from the Liverpool Eye and Diabetes Study (LEADS).

OBJECTIVE: There are limited data on the influence of ethnicity on diabetic retinopathy (DR). We sought to determine the distribution of DR by ethnic group in Australia. DESIGN: Clinic-based cross-sectional study. SETTING: Participants with diabetes in a defined geographical region of Sydney, Australia, who attended a tertiary retina referral clinic. PARTICIPANTS: The study recruited 968 participants. INTERVENTION: Participants underwent a medical interview and retinal photography and scanning. PRIMARY OUTCOME MEASURES: DR was defined from two-field retinal photographs. Diabetic macular oedema (DMO) was defined from spectral domain optical coherence tomography (OCT-DMO). The main outcomes were any DR, proliferative DR (PDR), clinically significant macular oedema (CSME), OCT-DMO and sight-threatening DR (STDR). RESULTS: There was high proportion of any DR (52.3%), PDR (6.3%), CSME (19.7%), OCT-DMO (28.9%) and STDR (31.5%) in people attending a tertiary retinal clinic. Participants of Oceanian ethnicity had the highest proportion of any DR and STDR (70.4% and 48.1%, respectively), while the lowest proportion was in participants of East Asian ethnicity (38.3% and 15.8%, respectively). Proportion of any DR and STDR in Europeans was 54.5% and 30.3%, respectively. Independent predictive factors for diabetic eye disease were ethnicity, longer duration of diabetes, higher glycated haemoglobin and higher blood pressure. Even after adjusting for risk factors, Oceanian ethnicity remained associated with twofold higher odds of any DR (adjusted OR 2.10, 95% CI 1.10 to 4.00) and all other forms of DR including STDR (adjusted OR 2.22, 95% CI 1.19 to 4.15). CONCLUSION: In people attending a tertiary retinal clinic, the proportion of people with DR varies among ethnic groups. The high proportion in persons of Oceanian ethnicity suggests a need for targeted screening of this at-risk group. In addition to traditional risks factors, ethnicity may be an additional independent predictor of DR.

Large, star-shaped retinal tear associated with orbital cosmetic filler.

PURPOSE: Presentation of a unique case of large, star-shaped retinal tear associated with orbital cosmetic filler injection. OBSERVATION: A 55-year-old healthy female presented to emergency department with sudden onset of blurred vision on her left eye occurred after an orbital cosmetic filler injection containing hyaluronic acid (HA) performed by an aesthetic nurse. On fundus examination, the left eye showed a mild - moderate, unusual appearance vitreous haze and a large, star-shaped retinal tear temporal to macula. Optical coherence tomography (OCT) examination demonstrated a normal foveal contour without any structural damage on the retinal layers. Vitrectomy, endolaser and silicon oil tamponade were performed. Visual acuity was maintained at 6/7.5 following silicon oil removal at 6 weeks after the initial surgery. CONCLUSIONS AND IMPORTANCE: In this particular case, immediate vitrectomy is key to avoid further complications such as retinal toxicity and detachment and to maintain optimal visual acuity. Importantly, facial cosmetic filler procedure should be performed by an adequately trained individual to avoid such complications.

CASE OF BILATERAL CHOROIDAL DETACHMENTS IN GRAFT-VERSUS-HOST DISEASE AND HYPOALBUMINAEMIA AFTER REDUCED-INTENSITY ALLOGENEIC BONE MARROW STEM CELL TRANSPLANTATION.

PURPOSE: To report a case of bilateral choroidal detachments in a patient with myelodysplasia who developed graft-versus-host disease and hypoalbuminemia after allogeneic bone marrow transplantation. METHODS: Case report imaged with ultra-widefield color photographs and B-scans. RESULTS: The patient presented with a 3-day history of bilateral visual deterioration, associated with right eye floaters. Fundus examination revealed choroidal detachments in all four quadrants associated with serous retinal detachment in the right eye and in the inferotemporal and inferonasal quadrant of the left eye. Medical history included allogeneic bone marrow transplantation for myelodysplastic syndrome seven months prior and development of symptoms of graft-versus-host disease three weeks prior. His serum albumin and protein levels were severely low. The detachments subsequently resolved with treatment of the hypoalbuminemia and low protein. CONCLUSION: Choroidal detachment is a possible complication of hypoalbuminemia and graft-versus-host disease. Hypoalbuminemia causing a reduction in the gradient for transscleral diffusion of albumin or graft-versus-host disease-related immune reaction is a possible mechanism of this complication.

Endophthalmitis: Changes in Presentation, Management and the Role of Early Vitrectomy.

Endophthalmitis is a sight-threatening condition, and its timely and appropriate management is essential in preventing permanent vision loss. Recent changes in clinical practice in endophthalmitis and advances in modern vitreoretinal surgery may limit the applicability of established randomised clinical trial evidence to current management. This review discusses the epidemiology, pathophysiology, changing patient presentation, diagnosis and advances in the management of endophthalmitis, presenting the existing literature on this topic and results from Sydney Eye Hospital.

Prevalence of Vitreoretinal Interface Disorders in an Australian Population: The Blue Mountains Eye Study.

Purpose: To describe the prevalence, risk factors, and associations of vitreoretinal interface (VRI) abnormalities in a population-based study of older adults. Design: Cross-sectional analysis of cohort study participants. Participants: Of the 1149 participants (mean age, 76.1 ± 6.9 years) in the 15-year Blue Mountains Eye Study follow-up examination from 2007 through 2009, 905 (1791 eyes) had gradable time-domain or spectral-domain OCT scans of the macula from at least 1 eye. Methods: OCT scans were graded according to the International Vitreomacular Traction Study Group classification system of VRI abnormalities. Best-corrected visual acuity (BCVA) was recorded. Main Outcome Measures: Prevalence of VRIs. Results: Overall, 451 participants showed any VRI abnormality (49.8%). Prevalence of VRI abnormality by person was: vitreomacular adhesion (VMA), 33.6%; vitreomacular traction (VMT), 1.6%; epiretinal membrane (ERM), 21.4%; full-thickness macular hole (FTMH), 0.7%; and lamellar macular hole (LMH), 0.7%. Twenty-two percent of VMAs were focal, and 78% were broad based; 76% of VMTs were focal, and 24% were broad based. All FTMHs observed were large (>400 µm), with mean aperture size of 573 µm (range, 459-771 µm). Increased age was associated with higher ERM and lower VMA prevalence (P < 0.001 for both). Pseudophakia and myopia were associated with ERM (age- and sex-adjusted odds ratios [ORs], 1.48 [95% confidence interval (CI), 1.01-2.17] and 1.72 [95% CI, 1.05-2.81], respectively). Moderate or severe ERM and FTMH were associated with worse BCVA of 9.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (95% CI, 3.4-15.0 ETDRS letters; P = 0.008) and 26.0 ETDRS letters (95% CI, 10.9-41.1 ETDRS letters; P = 0.001), respectively. Conclusions: The prevalence of VRI abnormalities is high in older individuals. Epiretinal membrane was associated with increasing age, pseudophakia, and myopia. Epiretinal membrane and FTMH may account for significant visual loss in the affected eye. This study provided useful population-based data on the prevalence of VRI abnormalities in older individuals.

Efficacy of Topical Carbonic Anhydrase Inhibitors in Reducing Duration of Chronic Central Serous Chorioretinopathy.

Purpose: Topical carbonic anhydrase inhibitors (CAIs) can influence retinal fluid distribution, but their role in treating central serous chorioretinopathy (CSCR) has not been studied. We examined the efficacy of a topical CAI (dorzolamide) in treating chronic CSCR. Methods: Prospective, nonrandomized, controlled intervention study of patients with chronic CSCR of at least 3 months duration. Observed controls (n = 15) were recruited consecutively from 2016 to 2017; treated cases (n = 18) were recruited from 2018 to 2019. Controls were observed without active intervention, whereas treated cases were treated with topical dorzolamide for 3 months. The study end points were change in central macular thickness (CMT), change in best corrected visual acuity (BCVA), and proportion of eyes achieving complete resolution of subretinal fluid (SRF). All end points were at 3 months. Results: Treated patients who received topical CAI had greater reduction in CMT (-145.6 µm, 95% confidence interval [CI] -170.5 to -120.7) compared to observed controls (-45.1 µm, 95% CI -65.3 to -25.1) at the main study end point of 3 months (P = 0.015). A higher proportion of treated patients achieved complete resolution of SRF compared to observed controls (77.8% vs. 40.0%, P = 0.04) at 3 months. However, change in BCVA at 3 months was similar in both groups (P = 0.12). Conclusions: Topical CAI resulted in more rapid reduction of CMT compared to observation. These results, if confirmed in other studies, suggest topical CAI may be a viable treatment option for patients with chronic CSCR. Translational Relevance: Topical CAI is used to treat a number of retinal disorders, and may be a novel treatment option for chronic CSCR.

Acylcarnitine Abnormalities Implicate Mitochondrial Dysfunction in Patients With Neovascular Age-Related Macular Degeneration.

Purpose: Abnormalities in lipid metabolism are implicated in age-related macular degeneration (AMD), but the pathways involved remain unclear. We assessed whether acylcarnitine concentrations, a marker of lipid and mitochondrial metabolism, differed between patients with AMD and controls. Methods: In this cross-sectional case-control study, cases (n = 81) had neovascular AMD and controls (n = 79) had cataract with no other ocular pathology. Participants were recruited from eye clinics in Western Sydney, Australia, between 2016 and 2018. Plasma blood samples were collected and liquid chromatography mass spectrometry analyses performed to identify acylcarnitine concentrations. Acylcarnitine levels were adjusted for age, gender and smoking in multivariable models. Confirmation of key acylcarnitine identities was conducted using high mass accuracy liquid chromatography-tandem mass spectrometry. Results: After multivariable adjustment, C2-carnitine (acetylcarnitine) levels were significantly lower in patients with neovascular AMD compared to controls (0.810 ± 0.053 (standard error) compared to 1.060 ± 0.053), p = 0.002). C18:2-DC carnitine (a dicarboxylic acylcarnitine with a 18 carbon side chain and 2 double bonds), levels were significantly higher in patients with neovascular AMD compared to controls (1.244 ± 0.046 compared to 1.013 ± 0.046), p = 0.001). Other acylcarnitines examined were not significantly different between cases and controls. Conclusions: Reduced plasma levels of C2-carnitine (acetylcarnitine) and increased plasma levels of C18:2-DC carnitine were observed in patients with neovascular AMD compared to controls. These findings suggest mitochondrial dysfunction could be involved in the pathogenesis of neovascular AMD.

New anti-hyperglycaemic agents for type 2 diabetes and their effects on diabetic retinopathy.

There has been an increase in the range of non-insulin anti-hyperglycaemic agents used to treat type 2 diabetes. With the globally rising rates of type 2 diabetes and complications such as diabetic retinopathy, it is important for ophthalmologists to be aware of these new agents and their impacts on diabetic retinopathy and diabetic macular oedema. We conducted a review of the literature to determine if there were any beneficial or harmful effects of the currently used anti-hyperglycaemic agents on diabetic retinopathy or diabetic macular oedema. Our review of the current literature found that apart from thiazolidinediones, anti-hyperglycaemic agents have been reported to have beneficial or neutral effects on diabetic eye complications. Thiazolidinediones (pioglitazone is the only one currently available) have been linked to incident or worsening diabetic macular oedema, although the rate is believed to be low. Glucagon-like peptide 1 (GLP1) agonists (incretins) in general are beneficial except semaglutide which is associated with increased rates of diabetic retinopathy complications. These results have implications for selection of anti-hyperglycaemic agents for patients with diabetic retinopathy or macular oedema. Further studies need to be conducted to identify if reported beneficial effects are independent of the impact of glycaemic control. Early worsening of retinopathy with tight glycaemic control should also be noted in interpretation of future studies.

Profile of a population-based diabetic macular oedema study: the Liverpool Eye and Diabetes Study (Sydney).

PURPOSE: The population prevalence of diabetic macular oedema (DME) is unclear. Previous estimates have depended on photographic grading of clinically significant macular oedema, which is subjective and has resulted in widely varying estimates. With the advent of optical coherence tomography (OCT), the presence and severity of DME can now be assessed objectively and accurately. METHODS: The Liverpool Eye and Diabetes Study (LEADS) is a cross-sectional population-based study of patients with type 1 and type 2 diabetes in a multi-ethnic region of Sydney, Australia, to determine the population prevalence of OCT-defined DME, how this varies by ethnicity and association with systemic factors. This report describes the rationale, methodology and study aims. RESULTS: To date 646 patients out of an expected sample size of 2000 have been recruited. Baseline data are presented for patients with type 1 (n=75, 11.8%) and type 2 (n=562, 88.2%) diabetes recruited to date. Patients with type 1 diabetes were younger (39.5vs60.7 years), with longer duration of diabetes (18.1vs11.7 years), slightly worse glycaemic control (HbA1c 9.0vs8.3), and less likely to have hypertension (30.7vs71.4%), hypercholesterolaemia (33.3vs74.6%) and obesity (31.1vs51.5%, respectively, all p<0.05). CONCLUSIONS: The LEADS will provide objective estimates of the population prevalence of DME, how this varies with ethnicity and associations with systemic disease.

Early Pars Plana Vitrectomy for Treatment of Acute Infective Endophthalmitis.

PURPOSE: To evaluate the efficacy and safety of early pars plana vitrectomy (PPV) for the treatment of acute infective endophthalmitis, and identify prognostic factors for better visual outcome. DESIGN: Retrospective cohort study. METHODS: Consecutive patients who underwent early PPV within 72 hours of presentation for the treatment of acute infective bacterial endophthalmitis and presented to a large tertiary referral center in New South Wales, Australia, between January 2009 and December 2013 were included. Changes in best-corrected visual acuity (VA) from baseline to 1 year were examined. RESULTS: A total of 64 patients were included. The inciting events were cataract surgery (53%), intravitreal injection (36%), trabeculectomy (3%), and endogenous (3%). The mean VA improved from 3.1 logMAR (hand motion) at baseline to 1.02 (approximately 20/200) at 1 year, with 42% achieving final VA equal to or better than 0.477 logMAR (20/60) following early PPV. Positive prognostic factors were negative microbial cultures (P < 0.01) and etiology of post-cataract surgery (P < 0.01). In multivariable analyses adjusting for age and prognostic factors, patients with baseline VA of light perception and hand motion achieved greater visual gains than those with counting fingers, with gains of logMAR of -2.68, -2.09, and -0.85, respectively (P < 0.0001). CONCLUSIONS: Most patients who undergo early PPV experience substantial VA improvement. Negative microbial cultures and endophthalmitis after cataract surgery were associated with better final visual outcome. Patients with presenting VA of light perception or hand motion achieved higher visual gains than those with counting fingers, suggesting the possibility that early PPV may be beneficial in both groups.

Metabolomics of Diabetic Retinopathy.

PURPOSE OF REVIEW: Metabolomics is the study of dysregulated metabolites in biological materials. We reviewed the use of the technique to elucidate the genetic and environmental factors that contribute to the development of diabetic retinopathy. RECENT FINDINGS: With regard to metabolomic studies of diabetic retinopathy, the field remains in its infancy with few studies published to date and little replication of results. Vitreous and serum samples are the main tissues examined, and dysregulation in pathways such as the pentose phosphate pathway, arginine to proline pathway, polyol pathway, and ascorbic acidic pathways have been reported. Few studies have examined the metabolomic underpinnings of diabetic retinopathy. Further research is required to replicate findings to date and determine longitudinal associations with disease.

Mini Review: Changes in the Incidence of and Progression to Proliferative and Sight-Threatening Diabetic Retinopathy Over the Last 30 Years.

PURPOSE: Diabetic retinopathy is a leading cause of blindness worldwide. The last 3 decades have seen major improvements in glycemic and blood pressure control as well as the introduction of national screening programs, and we sought to determine if rates of proliferative diabetic retinopathy have changed as a result. METHODS: We conducted a systematic review to determine whether the incidence and progression rates of proliferative diabetic retinopathy and sight-threatening retinopathy have changed, focusing on large population-based studies with objective assessment of diabetic retinopathy. RESULTS: Comparisons across different studies is problematic due to different baseline retinopathy severity, different reported outcomes and different follow-up periods, but within these constraints certain trends could be identified. This review provides evidence that the incidence and progression of these conditions has reduced by approximately 2-3 fold over the last 3 decades. CONCLUSION: These results have implications for current diabetic retinopathy screening guidelines and has identified future areas where research could be improved.

Vitrectomy for diabetic macular edema: a systematic review and meta-analysis.

OBJECTIVE: To systematically review, and perform meta-analysis on, the available data regarding the efficacy of vitrectomy for diabetic macular edema. DESIGN: Systematic review and meta-analysis of published randomized controlled trial data. METHODS: We searched PubMed and the Cochrane database for randomized, controlled trials investigating vitrectomy for diabetic macular edema. Structural (foveal thickness) and functional (visual acuity) outcomes were used as the primary outcome measures. RESULTS: Eleven studies met the criteria for inclusion in this review: these studies were heterogenous in their experimental and control interventions, follow-up period, and eligibility criteria. Seven studies compared vitrectomy with the natural history of diabetic maculopathy, with laser, or with intravitreal corticosteroid injection. Four studies compared vitrectomy with internal limiting membrane peeling to vitrectomy alone. One of the latter 4 studies was the only to investigate vitrectomy in patients with vitreomacular traction. Meta-analysis suggests a structural, and possibly functional, superiority of vitrectomy over observation at 6 months. Vitrectomy also appears superior to laser in terms of structural, but not functional, outcomes at 6 months. At 12 months, vitrectomy offers no structural benefit and a trend toward inferior functional outcomes when compared with laser. CONCLUSIONS: There is little evidence to support vitrectomy as an intervention for diabetic macular edema in the absence of epiretinal membrane or vitreomacular traction. Although vitrectomy appears to be superior to laser in its effects on retinal structure at 6 months, no such benefit has been proved at 12 months. Furthermore, there is no evidence to suggest a superiority of vitrectomy over laser in terms of functional outcomes.

Diagnosis and interventions for central serous chorioretinopathy: review and update.

Most acute cases of central serous chorioretinopathy resolve spontaneously with minimal visual impairment. The small percentage of eyes developing chronic or recurrent disease that do warrant treatment is often difficult to control. Emergent investigations and treatments have added to the established options available to manage these cases. Optical coherence tomography has proved valuable for both imaging subtle fundoscopic findings and monitoring disease progression. Fluorescein angiography aids identification of pigment epithelial leaks and targets the use of argon laser treatment if outside the fovea. Fluorescein angiography also assists differentiation from other choroidal pathologies such as choroidal neovascularization and polypoidal choroidal vasculopathy. Where the diagnosis is uncertain, indocyanine green angiography can demonstrate classic midphase hyperpermeability. This is also useful to guide the application of photodynamic therapy. Newer treatments such as intravitreal anti-vascular endothelial growth factor are as yet unproven.

Acute idiopathic maculopathy with coxsackievirus infection.

PURPOSE: To report a case of visual loss immediately after hand, foot, and mouth disease and demonstrate the high-resolution optical coherence tomography findings. METHODS: A retrospective case report of a 19-year-old nursery worker with resolving hand, foot, and mouth disease and acute unilateral visual loss. RESULTS: The clinical features were characteristic of unilateral acute idiopathic maculopathy. High-resolution optical coherence tomography demonstrated highly reflective subretinal material at the macula of one eye with disruption of the photoreceptor inner segment/outer segment junction. Vision remained poor for 4 weeks when there was rapid recovery coinciding with reconstitution of the inner segment/outer segment junction on optical coherence tomography. CONCLUSION: Unilateral acute idiopathic maculopathy may be caused by Coxsackievirus infection. Optical coherence tomography and clinical findings suggest an acute viral retinal pigment epitheliitis to be the main pathologic feature.

Does unintentional macular translocation after retinal detachment repair influence visual outcome?

BACKGROUND: To document the occurrence of postoperative macular translocation after retinal detachment repair and discuss its influence on visual outcome. DESIGN: Retrospective case series in a tertiary care setting. PARTICIPANTS: Five eyes of five patients presenting to our clinic with macula-off rhegmatogenous retinal detachment. METHODS: All patients underwent surgical repair of the retinal detachment, with regular postoperative follow-up, including macular optical coherence tomography and fundus autofluorescence. MAIN OUTCOME MEASURES: Visual acuity and subjective visual symptoms in patients with anatomically successful retinal detachment repair, in whom inadvertent macular translocation was noted. RESULTS: Our series demonstrates the presence of unintentional macular translocation after retinal detachment repair, detected by fundus autofluorescence imaging. In contrast to previous reports, we document inadvertent macular translocation in one patient after scleral buckling surgery. In each case, the retina was fully reattached postoperatively and no other complications were identified. There was variability in the symptoms and objective visual outcomes after surgery. CONCLUSIONS: Inadvertent macular translocation can occur following repair of macula-off retinal detachment, and may be a significant contributor to poorer visual outcome after retinal detachment, despite objective surgical success.

Evolution of reticular pseudodrusen.

AIMS: To report observations relating to the clinical recognition and possible basis of reticular pseudodrusen (RPD). METHODS: This retrospective study reports the evolution of RPD in 166 patients who had follow-up of over 1 year using multiple imaging techniques. Mean age when first seen was 73.3 years and the mean period of observation was 4.9 years (range 1-18 years). Associated macular changes were recorded. RESULTS: RPD were first identified in the upper fundus as a reticular network, which then became less obvious, developing a diffuse yellowish appearance. RPD also faded around choroidal neovascularisation (CNV). RPD therefore could be transient but the pattern often remained visible outside the macula or nasal to the discs. Manifestations of age-related macular degeneration (AMD) were present in nearly all eyes and there was a particularly high association with CNV (52.1%). In one clinicopathological case abnormal material was found in the subretinal space. CONCLUSIONS: The prevalence of RPD may be underestimated because their recognition depends upon the imaging method used, the area of fundus examined and the confusion with typical drusen. The pathology of one eye suggests that RPD may correspond to material in the subretinal space.