Clinical performance of predicting late age-related macular degeneration development using multimodal imaging.

BACKGROUND: To examine whether the clinical performance of predicting late age-related macular degeneration (AMD) development is improved through using multimodal imaging (MMI) compared to using colour fundus photography (CFP) alone, and how this compares with a basic prediction model using well-established AMD risk factors. METHODS: Individuals with AMD in this study underwent MMI, including optical coherence tomography (OCT), fundus autofluorescence, near-infrared reflectance and CFP at baseline, and then at 6-monthly intervals for 3-years to determine MMI-defined late AMD development. Four retinal specialists independently assessed the likelihood that each eye at baseline would progress to MMI-defined late AMD over 3-years with CFP, and then with MMI. Predictive performance with CFP and MMI were compared to each other, and to a basic prediction model using age, presence of pigmentary abnormalities, and OCT-based drusen volume. RESULTS: The predictive performance of the clinicians using CFP [AUC = 0.75; 95% confidence interval (CI) = 0.68-0.82] improved when using MMI (AUC = 0.79; 95% CI = 0.72-0.85; p = 0.034). However, a basic prediction model outperformed clinicians using either CFP or MMI (AUC = 0.85; 95% CI = 0.78-91; p ≤ 0.002). CONCLUSIONS: Clinical performance for predicting late AMD development was improved by using MMI compared to CFP. However, a basic prediction model using well-established AMD risk factors outperformed retinal specialists, suggesting that such a model could further improve personalised counselling and monitoring of individuals with the early stages of AMD in clinical practice.

Acute effects of caffeine and glucose intake on retinal vessel calibres in healthy volunteers.

PURPOSE: To evaluate the acute effects of caffeine and glucose intake on retinal vascular calibre of healthy adults. METHODS: This prospective crossover study was conducted at the Centre for Eye Research Australia (Melbourne, Australia). Standardized doses of 300 mg caffeine (approximately 3 cups coffee), 30 g glucose or 300 ml of water, were each given to 19 healthy subjects on separate days. Retinal photographs and blood pressure measurements were taken at baseline, 30-, 60- and 120-min after ingestion of each solution. Central retinal artery and vein equivalents (CRAE, CRVE) and the arterio-venule ratio were measured using computer-assisted software. The mean retinal vascular calibre measurements were compared between pre- and post-ingestion images. RESULTS: After caffeine intake, significant reductions were observed in mean CRAE of - 9.3 µm, - 10.4 µm and - 8.5 µm and CRVE of - 16.9 µm, - 18.7 µm and - 16.1 µm at 30-, 60- and 120-min after intake when compared with baseline (p ≤ 0.002 for all; paired t test). No significant changes were observed in mean retinal vascular calibre measurements after intake of either glucose or water when compared to baseline (p ≥ 0.072 for all). When controlling for baseline characteristics and blood pressure measurements, only caffeine intake had a significant effect on reducing both CRAE and CRVE at all time points post ingestion (p ≤ 0.003 for all, multiple linear regression model). CONCLUSION: Caffeine is associated with an acute vasoconstrictive effect on retinal arterioles and venules in healthy subjects. Factors other than blood pressure-induced autoregulation play a significant role in caffeine-associated retinal vasoconstriction.

The association between intravitreal ranibizumab therapy and serum cytokine concentrations in patients with diabetic macular edema.

Aim: To investigate the association between intravitreal ranibizumab therapy and serum cytokine concentrations in patients with diabetic macular edema (DME). Methods: Twenty-five patients with center-involved DME were recruited prospectively. Serum samples were collected from the patients before and 4 weeks after two ranibizumab injections. The levels of 32 cytokines at these two time points were assessed using a multiplex array assay. Results: Following two ranibizumab injections, there was a statistically significant decrease in the median [interquartile range] levels of Interleukin 1-1beta (IL-1ß) from 5.56 [3.6, 8.75] to 2.33 [1.51, 2.89], Interleukin 13 (IL-13) from 4.30 [1.84, 18.55] to 0.38 [0.38, 0.78], granulocyte-colony stimulating factor (G-CSF) from 64.65 [42.9, 108] to 37.8 [27.3, 46.37], Interferon gamma (IFN-γ) from 241 [103.33, 753.4] to 94.4626 [42.04, 118.58], Interferon gamma-induced protein 10 (IP-10) from 234.68 [144.16, 285.98] to 158.73 [94.71, 198.64], Macrophage Inflammatory Protein-1 alpha (MIP-1α) from 3.65 [2.62, 11.02] to 1.41 [0.94, 1.88], and Tumor necrosis factor- alpha (TNF-α) from 131.09 [100.68,28 240.27] to 45.19 [24.04, 68.55]. There was a statistically significant increase in the levels of Interleukin 9 (IL-9) from 0.76 [0.76, 7.03] to 19.67 [5.36 27.76], Macrophage Inflammatory Protein-1 beta (MIP-1ß) from 0.28 [0.28, 30 0.28] to 6.79 [I3.74, 14.16], Vascular endothelial growth factor (VEGF) from 2.55 [2.55, 2.55] to 25.24 [14.51, 41.73], and soluble vascular endothelial growth factor -1 (sVEGFR-1) from 333.92 [204.99, 440.43] to 500.12 [38.7, 786.91]. A Bonferroni-corrected p value of 0.00156 was considered statistically significant. Conclusions: In patients with DME, intravitreal ranibizumab therapy appears to influence the serum levels of a range of cytokines. After two injections, intravitreal ranibizumab therapy appears to be associated with a significant decrease in inflammatory mediators and a rise in VEGF and sVEGFR1.

A treat and extend protocol with Aflibercept for cystoid macular oedema secondary to central retinal vein occlusion - an 18-month prospective cohort study.

BACKGROUND: To evaluate the safety and efficacy of a treat-and-extend protocol of aflibercept for cystoid macular oedema (CMO) secondary to central retinal vein occlusion (CRVO). METHODS: Twenty patients with CMO secondary to CRVO were included in this prospective cohort study. After 3 loading 4-weekly injections, treatment intervals were increased by 2 weeks if there was no clinical activity, to a maximum of 12 weeks. If clinical activity recurred or persisted, the interval between injections was shortened by 2 weeks, to a minimum of 4 weeks. Main outcome measures were change in visual acuity and the proportion of patients gaining 15 or more Early Treatment of Diabetic Retinopathy Study (ETDRS) letters from baseline at 6, 12 and 18 months. RESULTS: Mean BCVA gain from baseline was 19.7 ± 13.8, 22.2 ± 13.9 and 21.9 ± 15.8 ETDRS letters at 6, 12 and 18 months, respectively. Sixty-five percent of patients gained 15 or more ETDRS letters at 6 months, increasing to 70.6% at 12 and 18 months. Patients received 5.0 [4.0 to 6.0], 8.5 [8.0 to 10.3] and 11.0 [9.0 to 12.5] injections by 6, 12 and 18 months, respectively. CONCLUSIONS: The visual outcomes achieved with a treat-and-extend protocol in this study were similar to the pivotal trials of aflibercept for CMO secondary to CRVO, which used monthly and then as-needed protocols. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, registration number ACTRN12615000417583, 01/05/2015.

Diabetic retinopathy progression 6 months post-cataract surgery with intravitreous bevacizumab vs triamcinolone: A secondary analysis of the DiMECAT trial.

IMPORTANCE: Diabetic retinopathy (DR) may progress following cataract surgery due to surgery-induced inflammation. The effect of intravitreal bevacizumab (BVB) and triamcinolone acetonide (TCA), which have differing anti-inflammatory properties, on DR progression following cataract surgery has not been reported. BACKGROUND: To report the progression of DR in diabetic patients undergoing cataract extraction treated with intravitreal BVB or TCA during the surgery. DESIGN: Post hoc analysis of 6-month data from a prospective, randomized, double-masked clinical trial. PARTICIPANTS: Diabetic patients with clinically significant cataract and fovea involving diabetic macular oedema (DME), or a recent history of DME. METHODS: Participants were randomly allocated 1:1 to receive intravitreal BVB 1.25 mg or TCA 4 mg during and post-cataract surgery as needed. The rate of DR progression between groups was compared. MAIN OUTCOME MEASURES: DR progression. RESULTS: There were 61 eyes included. Patients receiving BVB were older than those receiving TCA (70.2 vs 64.3 years; P < .05). Three participants (10.7%) in the BVB and three (9.09%) in the TCA group had a one-step progression, while none in BVB and only one (3%) in the TCA group demonstrated two-step DR progression. In the majority of these patients, DR progression was from mild to moderate non-proliferative diabetic retinopathy. CONCLUSION AND RELEVANCE: In this study, BVB and TCA groups had a similar, and lower rate of DR progression compared to previous studies where no adjunctive treatment was administered, suggesting that patients with DME may benefit from either intraoperative intravitreous BVB or TCA injection to reduce the risk of DR progression following cataract surgery.

Subthreshold Nanosecond Laser Intervention in Age-Related Macular Degeneration: The LEAD Randomized Controlled Clinical Trial.

PURPOSE: There is an urgent need for a more effective intervention to slow or prevent progression of age-related macular degeneration (AMD) from its early stages to vision-threatening late complications. Subthreshold nanosecond laser (SNL) treatment has shown promise in preclinical studies and a pilot study in intermediate AMD (iAMD) as a potential treatment. We aimed to evaluate the safety of SNL treatment in iAMD and its efficacy for slowing progression to late AMD. DESIGN: The Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study is a 36-month, multicenter, randomized, sham-controlled trial. PARTICIPANTS: Two hundred ninety-two participants with bilateral large drusen and without OCT signs of atrophy. METHODS: Participants were assigned randomly to receive Retinal Rejuvenation Therapy (2RT®; Ellex Pty Ltd, Adelaide, Australia) SNL or sham treatment to the study eye at 6-monthly intervals. MAIN OUTCOME MEASURES: The primary efficacy outcome was the time to development of late AMD defined by multimodal imaging (MMI). Safety was assessed by adverse events. RESULTS: Overall, progression to late AMD was not slowed significantly with SNL treatment compared with sham treatment (adjusted hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.33-1.14; P = 0.122). However, a post hoc analysis showed evidence of effect modification based on the coexistence of reticular pseudodrusen (RPD; adjusted interaction P = 0.002), where progression was slowed for the 222 participants (76.0%) without coexistent RPD at baseline (adjusted HR, 0.23; 95% CI, 0.09-0.59; P = 0.002), whereas an increased progression rate (adjusted HR, 2.56; 95% CI, 0.80-8.18; P = 0.112) was observed for the 70 participants (24.0%) with RPD with SNL treatment. Differences between the groups in serious adverse events were not significant. CONCLUSIONS: In participants with iAMD without MMI-detected signs of late AMD, no significant difference in the overall progression rate to late AMD between those receiving SNL and sham treatment were observed. However, SNL treatment may have a role in slowing progression for those without coexistent RPD and may be inappropriate in those with RPD, warranting caution when considering treatment in clinical phenotypes with RPD. Our findings provide compelling evidence for further trials of the 2RT® laser, but they should not be extrapolated to other short-pulse lasers.

Paracentral acute middle maculopathy as a finding in patients with severe vision loss following phacoemulsification cataract surgery.

IMPORTANCE: Paracentral acute middle maculopathy (PAMM) diagnosed by spectral domain optical coherence tomography (SD-OCT) in patients with poor visual outcome post cataract surgery. BACKGROUND: Case series of severe vision loss due to PAMM after cataract surgery. DESIGN: Retrospective case series. PARTICIPANTS: Cases from five surgical centres in Victoria, Australia. METHODS: Retrospective analysis of cases with unexplained 'patch-off' vision loss post cataract surgery. All patients in our cohort had PAMM and presumed diagnosis of central or transient retinal artery occlusion. MAIN OUTCOME MEASURES: A review of the patient histories focusing on pre-operative ocular and systemic vascular risk factors, anaesthetic and operative factors. RESULTS: Ten cases were included. All patients had 6/72 Snellen visual acuity or worse noted on day one post surgery. Three patients had features of central retinal artery occlusion consisting of retinal pallor with a 'cherry red' macula but absent relative afferent pupillary defect. Seven had no features of retinal pallor or attenuation of retinal arterioles. On SD-OCT, all eyes had evident PAMM. Six patients had a history of cardiovascular disease or blood dyscrasia. CONCLUSIONS AND RELEVANCE: PAMM should be considered in patients with 'patch off' visual loss and absence of other fundal signs. We hypothesise that spasm or transient occlusion of central retinal artery leads to arterial hypoperfusion with subsequent ischaemia or infarction of the retina. Underlying arterial disease may have led to pre-existing hypoperfusion that may have been further compromised by raised intraocular pressure during the procedure itself or via raised orbital pressure from the anaesthesia.

IMPLICATION OF RECURRENT OR RETAINED FLUID ON OPTICAL COHERENCE TOMOGRAPHY FOR VISUAL ACUITY DURING ACTIVE TREATMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION WITH A TREAT AND EXTEND PROTOCOL.

PURPOSE: Assess the correlation between optical coherence tomography findings and change in vision for patients receiving "treat and extend" protocol ranibizumab for neovascular age-related macular degeneration. METHODS: Optical coherence tomography analysis and best-corrected visual acuity (BCVA) change: mild = 5 to 9 letters, moderate = 10 to 14 letters, and severe ≥15 letters. RESULTS: A total of 103 eyes (99 patients, 63% female, 65-91 years) followed for 20.8 ± 4.9 months. By 12 months, there were 1.38 ± 0.59 instances of intraretinal fluid (IRF)/subretinal fluid recurrence on optical coherence tomography and 1.25 ± 1.00 instances of BCVA loss (≥5 letters) per patient. When BCVA was lost, IRF/subretinal fluid was present in 37.3% of cases. Occurrences of severe BCVA loss were less likely to recover vision than when BCVA loss was mild (5.9% vs. 75.6%, P = 0.001). New occurrence of IRF (33.9%) or subretinal fluid (29.6%) was more likely to lead to BCVA loss, compared with dry (16.6%) or persistent IRF (11.9%) or persistent subretinal fluid (14%, P < 0.001). With persistent fluid, any new loss of vision had a lower chance of recovery than when fluid was new in onset (64.3% vs. 85.3%, P = 0.04). CONCLUSION: During ranibizumab treatment, vision can decrease without signs of fluid. When fluid is present, IRF is associated with poorer vision. New occurrence of any fluid on optical coherence tomography is likely to lead to vision loss, but small amounts of persistent fluid can be tolerated without compromising vision.

Diabetic Macular Edema at the time of Cataract Surgery trial: a prospective, randomized clinical trial of intravitreous bevacizumab versus triamcinolone in patients with diabetic macular oedema at the time of cataract surgery - preliminary 6 month results.

BACKGROUND: To compare visual and anatomical outcomes between intravitreous bevacizumab (BVB, Avastin) and triamcinolone (TA, Triesence) when administered at the time of cataract surgery in patients with diabetic macular oedema (DME). DESIGN: Prospective, single-masked, randomized clinical trial at The Royal Victorian Eye and Ear Hospital, Melbourne. PARTICIPANTS: Patients with clinically significant cataract and either centre-involving DME or DME treated within the previous 24 months. METHODS: Participants were randomized 1:1 to receive intravitreous BVB 1.25 mg or TA 4 mg during cataract surgery, and at subsequent review if required over 6 months. MAIN OUTCOME MEASURES: Change in central macular thickness (CMT) and best corrected visual acuity at 6 months. RESULTS: Forty-one patients (mean age 66.4 years, 73.2% male) were recruited. Visual acuity and CMT were similar between groups at baseline (P > 0.2).After six months, both groups gained vision (mean +21.4 letters in TA group P < 0.0001, +12.5 letters in BVB, P = 0.002), with no significant difference between groups (P = 0.085). In addition, 60.9% of eyes receiving TA achieved a VA of ≥6/12 compared to 73.3% in the BVB group (P = 0.501). However, only TA was associated with a sustained reduction in CMT (-43.8-µm reduction TA vs. +37.3-µm increase BVB, P = 0.006 over 6 months). Following surgery, additional injections were required in 70.6% of participants in the BVB group, compared to 16.7% in the TA group (P < 0.0001). Three patients in the TA group experienced a rise of IOP over 21 mmHg (12.5%) during the 6-month follow-up; BVB had no cases (P = 0.130). There were no cases of endophthalmitis in either group. CONCLUSIONS: When administered at the time of cataract surgery in patients with DME, at 6 months both TA and BVB improve visual acuity; however, only TA results in a sustained reduction in CMT. Further follow-up will determine whether this translates into better long-term visual outcomes in the TA group.

Anti-VEGF treatment in neovascular age-related macular degeneration: a treat-and-extend protocol over 2 years.

PURPOSE: To evaluate 2-year visual acuity outcome of a treat-and-extend protocol of anti-vascular endothelial growth factor treatment in age-related macular degeneration. METHODS: In this prospective cohort study, 120 age-related macular degeneration patients with choroidal neovascularization received 3 initial monthly ranibizumab or bevacizumab injections; monthly injections were continued until there was no choroidal neovascularization activity (subretinal/intraretinal fluid, loss of >5 letters, or persistent/recurrent retinal hemorrhage). When there was no choroidal neovascularization activity, the interval to the next visit/injection was extended by 2 weeks to a maximum of 12 weeks. In the presence of choroidal neovascularization activity, this interval was shortened by 2 weeks. Main outcome measures included the percentage losing <15 letters and the mean visual acuity change after 12 months and 24 months. RESULTS: Mean baseline visual acuity was 51.2 ± 12.1 Early Treatment Diabetic Retinopathy Study scores. Mean visual acuity change from baseline was +9.5 ± 10.9 and +8.0 ± 12.9 letters after 12 months and 24 months, respectively, with, on average, 8.6 ± 1.1 visits/injections in the first year and 5.6 ± 2.0 in the second year. After 12 months and 24 months, 97.5% and 95.0% of patients, respectively, lost <15 letters. CONCLUSION: The "inject-and-extend" protocol-with fewer injections and visits-delivered outcomes comparable to those of the pivotal clinical trials of monthly ranibizumab.

Polymorphisms in the APOE gene and the location of retinal fluid in eyes with neovascular age-related macular degeneration.

BACKGROUND: Previous reports suggest that the outcome of age-related macular degeneration treatment is dependent on variants in the apolipoprotein E (APOE) gene. We wish to establish if variants in this gene are associated with anatomical location of fluid within the macula on optical coherence tomography imaging before and after three anti-vascular endothelial growth factor treatments. METHODS: Patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration were prospectively enrolled and monitored over a 12-month period. Main outcome measures were logMAR best-corrected visual acuity and correlation of qualitative optical coherence tomography features (intraretinal fluid [IRF] and/or subretinal fluid) at baseline and after three anti-vascular endothelial growth factor injections with genetic variants of the APOE gene. RESULTS: One hundred and eighty-six eyes of 186 patients aged 79.4 years (range, 58-103 years). Subjects with an ε2 allele were more likely to have IRF at baseline compared with the eyes without (odds ratio: 2.98, 95% confidence interval: 1.22-7.29, P = 0.02). After 3 injections, 184 eyes remained. Of these, 114 of eyes (62.0%) were classified as "dry" on optical coherence tomography, whereas 48 eyes (26.1%) still had a component of IRF, and 22 (12.0%) had subretinal fluid alone. There was no statistically significant association between APOE variants and presence of persistent IRF, although there were almost double the number of subjects with ε2 (40%) who had persistent fluid compared with those with ε3/ε4 (23%) (P = 0.06). CONCLUSION: In patients with neovascular age-related macular degeneration, the presence of the ε2 allele of the APOE gene was associated with having IRF at baseline. Larger studies are required to determine if a greater proportion of those with the ε2 allele retain this fluid after three initial injections.

Variants in the VEGFA gene and treatment outcome after anti-VEGF treatment for neovascular age-related macular degeneration.

PURPOSE: To determine the association of genetic variants of the VEGFA gene with outcome of anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (AMD). DESIGN: A prospective cohort study. PARTICIPANTS: We included 201 consecutive patients receiving anti-VEGF injections for neovascular AMD. METHODS: Patients were followed over 12 months. They were treated with 3 initial monthly ranibizumab or bevacizumab injections. Thereafter, the decision to retreat was made by clinicians at each follow-up visit on the basis of retreatment criteria. Seven tagged single nucleotide polymorphisms (tSNPs) in the VEGFA gene were selected and examined. Multivariate data analysis was used to determine the role of each tSNP in treatment outcome. MAIN OUTCOME MEASURES: The influence of selected VEGFA tSNPs on visual acuity (VA) outcome at 6 months. RESULTS: Mean baseline VA was 51±17 Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores. Overall, the mean change in VA from baseline was +6.5±12, +4.4±13.4, and +2.3±14.6 letters at 3, 6, and 12 months, respectively. The tSNP rs3025000 was the only SNP significantly associated (P<1 × 10(-4)) with visual outcome at 6 months with multiple correction. The presence of the T allele (TC or TT genotypes) at this tSNP predicted a better outcome of +7 letters at 6 months compared with the CC genotype. In a subgroup analysis, presence of the T allele predicted a significantly higher chance of the patients belonging to the responder group (gain of ≥5 letters from baseline) after 3, 6, and 12 months treatment (odds ratio, 2.7, 3.5, and 2.4; 95% confidence interval, 1.46-5.07, 1.82-6.71, and 1.27-4.57, respectively) than any other outcome group. CONCLUSIONS: Pharmacogenetic association with anti-VEGF treatments may influence the visual outcomes in neovascular AMD. In patients with the T allele in tSNP rs3025000, there was a significantly better visual outcome at 6 months and a greater chance of the patients belonging to the responder group with anti-VEGF treatment at 3, 6, and 12 months. The VA outcomes of patients harboring the T allele at SNP rs3025000 were comparable with those of the pivotal clinical trials but with fewer injections, making the treatment perhaps more cost effective in certain subgroups of patients. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Genetic influences on the outcome of anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration.

PURPOSE: To determine the association of genetic variants in known age-related macular degeneration (AMD) risk-associated genes with outcome of anti-vascular endothelial growth factor (VEGF) treatment in neovascular AMD. DESIGN: Prospective cohort study. PARTICIPANTS: We enrolled 224 consecutive patients with neovascular AMD at the Royal Victorian Eye and Ear Hospital, Australia. METHODS: Patients were treated with 3 initial monthly ranibizumab or bevacizumab injections followed by 9 months of "as required" injections based on clinician's decision at each follow-up visit according to retreatment criteria. Seventeen single nucleotide polymorphisms (SNPs) in known AMD risk-associated genes including CFH (rs800292, rs3766404, rs1061170, rs2274700 and rs393955), HTRA1 (rs11200638), CFHR1-5 (rs10922153, rs16840639, rs6667243, and rs1853883), LOC387715/ARMS2 (rs3793917 and rs10490924), C3 (rs2230199 and rs1047286), C2 (rs547154), CFB (rs641153) and F13B (rs6003) were examined. Multivariate analysis was used to determine the role of each SNP in treatment outcome. MAIN OUTCOME MEASURES: The influence of selected SNPs on mean change in visual acuity (VA) at 12 months. RESULTS: Mean baseline VA was 51 ± 16.8 Early Treatment Diabetic Retinopathy Study letters. Overall, the mean change in VA from baseline was +3.2 ± 14.9 letters at 12 months. The AA (homozygote risk) genotype at rs11200638 - HTRA1 promoter SNP (P = 0.001) and GG (homozygote risk) genotype at rs10490924 (A69S) in LOC387715/ARMS2 (P = 0.002) were each significantly associated with poorer VA outcome at 12 months after multiple correction. Mean ± standard deviation change in VA from baseline in patients with AA genotype at rs11200638 was -2.9 ± 15.2 letters after 12 months compared with +5.1 ± 14.1 letters in patients with AG or GG genotypes at this SNP. Patients with either of these genotypes were also significantly more likely to lose >15 letters after 12 months. SNPs rs11200638 and rs10490924 were in high linkage disequilibrium (r(2) = 0.92). None of the other examined SNPs was associated with outcome. CONCLUSIONS: The HTRA1 promoter SNP (rs11200638) and A69S at LOC387715/ARMS2 were associated with a poorer visual outcome for ranibizumab or bevacizumab treatment in neovascular AMD, suggesting strong pharmacogenetic associations with anti-VEGF treatment. This finding could aid in applying more individualized treatment regimens based on patients' genotype to achieve optimal treatment response in AMD. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Five-year outcomes of eyes initially enrolled in the 2-year BEVORDEX trial of bevacizumab or dexamethasone implants for diabetic macular oedema.

BACKGROUND: The BEVORDEX trial compared outcomes of eyes with diabetic macular oedema (DMO) randomised to receive either intravitreal dexamethasone (DEX-) implant or bevacizumab over 2 years. We assessed long-term efficacy and safety outcomes 5 years from enrolment. METHODS: Patients received standard clinical care after they finished the study. Their files were reviewed for visual and anatomical outcomes, post-trial treatments and complications. RESULTS: Three-year and five-year data were available for 82% and 59% of eyes enrolled in the BEVORDEX study, respectively. Visual acuity gains at end of trial were generally lost by both treatment groups at 5 years but the macular thickness did not change from end of trial to 5 years. A similar proportion of eyes from each treatment group gained ≥10 letters at 5 years from enrolment in the BEVORDEX trial.Eyes that were initially randomised to the DEX-implant group had significantly fewer treatments but were more likely to develop proliferative diabetic retinopathy (PDR) over the 5-year period compared with eyes initially randomised to bevacizumab. The proportion of eyes that had cataract surgery by 5 years was similar between initial treatment groups. CONCLUSIONS: Eyes in the BEVORDEX trial had similar 5-year rates of cataract surgery, however, more eyes converted to PDR in the group initially treated with DEX-implant. Eyes that were initially treated for 2 years with either intravitreal DEX-implant of bevacizumab followed by standard of care had similar visual and anatomical outcomes at 5 years.

Retinal venular calibre dilatation after intravitreal ranibizumab treatment for neovascular age-related macular degeneration.

BACKGROUND: To describe the changes in retinal vascular calibre in response to intravitreal ranibizumab injections in patients with neovascular age-related macular degeneration. DESIGN: Prospective interventional case series. PARTICIPANTS: Treatment naïve patients with neovascular age-related macular degeneration were recruited over a 1-year period. METHODS: Each patient received three monthly intravitreal injections according to a 'loading dose'. Retinal arteriolar and venular calibre was measured from digital fundus photographs and summarized as central retinal artery equivalent and central retinal vein equivalent at baseline and 3 months. MAIN OUTCOME MEASURE: Central retinal artery equivalent and central retinal vein equivalent changes from baseline to 3 months. RESULTS: Seventy-four eyes of 71 patients had good quality images for grading vessel calibre at baseline and at 3 months in treated (study) eyes and 51 eyes of 51 patients had good quality images in fellow (control) eyes. Over 3 months, in study eyes treated with ranibizumab, there was a significant increase in central retinal vein equivalent over baseline (+6.20 µm, P = 0.005), but no significant change in central retinal artery equivalent (+0.86 µm, P = 0.55). In control eyes, there was no change in central retinal vein equivalent (-0.82 µm, P = 0.70) or central retinal artery equivalent (0.34 µm, P = 0.75). CONCLUSION: Intravitreal ranibizumab has a significant vasodilational effect on retinal venular calibre in eyes treated for neovascular age-related macular degeneration. The reason for this change is unclear, but may relate to changes in blood flow or inflammatory changes within the retina.

The prevalence estimates of macular telangiectasia type 2: the Melbourne Collaborative Cohort Study.

PURPOSE: The purpose of this study was to determine the prevalence estimates of macular telangiectasia type 2 in an Australian population based on nonmydriatic digital fundus photography. METHODS: Participants of the Melbourne Collaborative Cohort Study, initiated to investigate risk factors for common aging diseases, had nonmydriatic digital macular images taken from both eyes and graded for any macular abnormalities. Prevalence of the features suggestive of macular telangiectasia type 2 was assessed. RESULTS: Macular images from the 22,062 subjects with a mean age of 64.96 years (range, 47-85 years) were assessed. Of these images, 43,234 images were gradable (21,708 images of the right eye and 21,526 images of the left eye). Using only the grading features of the macular images taken by the nonmydriatic digital fundus photography, 5 subjects with signs consistent with bilateral macular telangiectasia type 2 in this population were found by the authors. Based on the Gass-Blodi staging of this disease, all (5) were determined to be in stages 2 and 3. CONCLUSION: In an Australian population, the prevalence estimates of macular telangiectasia type 2 were found to be 1 of 22,062 to 5 of 22,062 or 5 to 23 cases per 100,000 people in which disease was at least at stages 2 and 3.