Vision-Related Quality of Life and Ocular Parameters in End-Stage Renal Disease Patients Undergoing Hemodialysis.

Purpose: To evaluate the vision-related quality of life (VRQoL) of patients receiving hemodialysis through the assessment of the impact of vision impairment (IVI) questionnaire and ocular parameters, including best-corrected visual acuity (BCVA), intraocular pressure (IOP), and refraction as calculated by spherical equivalent (SE) of each eye. Methods: Fifty-one patients with end-stage renal disease undergoing hemodialysis at a single center were recruited, and a total of 77 eyes were evaluated. BCVA, IOP, and SE were evaluated before and after hemodialysis (within 30 min). Results: Of the 51 patients recruited, 13 (25%) were female, 37 (73%) were male, and one (2%) chose not to specify gender. The mean age was 61.85 ± 32 years. The mobility IVI score was correlated significantly with the presence of hypertension (P = 0.01), eye drop usage (P = 0.04), and gender (P = 0.04). Emotional IVI scores were correlated significantly with diabetes (P = 0.03) and hypertension (P < 0.01). IOP significantly correlated with the IVI overall score (P = 0.02), including the reading IVI subscale and the emotional IVI subscale. Several factors were associated with posthemodialysis ocular parameters, including predialysis ocular parameters, age, and hypertension (P < 0.05 for all). Conclusions: IOP significantly correlated with VRQoL in hemodialysis patients. Demographic variables such as diabetes status, hypertension, eye drop usage, and gender also significantly correlated with subsections of the IVI questionnaire. This study investigated the relationship between ocular parameters and VRQoL in hemodialysis patients, and future longitudinal research is needed to further elucidate the mechanisms.

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.

Real-world artificial intelligence-based opportunistic screening for diabetic retinopathy in endocrinology and indigenous healthcare settings in Australia.

This study investigated the diagnostic performance, feasibility, and end-user experiences of an artificial intelligence (AI)-assisted diabetic retinopathy (DR) screening model in real-world Australian healthcare settings. The study consisted of two components: (1) DR screening of patients using an AI-assisted system and (2) in-depth interviews with health professionals involved in implementing screening. Participants with type 1 or type 2 diabetes mellitus attending two endocrinology outpatient and three Aboriginal Medical Services clinics between March 2018 and May 2019 were invited to a prospective observational study. A single 45-degree (macula centred), non-stereoscopic, colour retinal image was taken of each eye from participants and were instantly screened for referable DR using a custom offline automated AI system. A total of 236 participants, including 174 from endocrinology and 62 from Aboriginal Medical Services clinics, provided informed consent and 203 (86.0%) were included in the analysis. A total of 33 consenting participants (14%) were excluded from the primary analysis due to ungradable or missing images from small pupils (n = 21, 63.6%), cataract (n = 7, 21.2%), poor fixation (n = 2, 6.1%), technical issues (n = 2, 6.1%), and corneal scarring (n = 1, 3%). The area under the curve, sensitivity, and specificity of the AI system for referable DR were 0.92, 96.9% and 87.7%, respectively. There were 51 disagreements between the reference standard and index test diagnoses, including 29 which were manually graded as ungradable, 21 false positives, and one false negative. A total of 28 participants (11.9%) were referred for follow-up based on new ocular findings, among whom, 15 (53.6%) were able to be contacted and 9 (60%) adhered to referral. Of 207 participants who completed a satisfaction questionnaire, 93.7% specified they were either satisfied or extremely satisfied, and 93.2% specified they would be likely or extremely likely to use this service again. Clinical staff involved in screening most frequently noted that the AI system was easy to use, and the real-time diagnostic report was useful. Our study indicates that AI-assisted DR screening model is accurate and well-accepted by patients and clinicians in endocrinology and indigenous healthcare settings. Future deployments of AI-assisted screening models would require consideration of downstream referral pathways.

Response to correspondence from Koerner and colleagues concerning our paper entitled: The effect of diluting povidone-iodine on bacterial growth associated with speech.

Clinicians adopt varying strategies for antisepsis with PI, which to this day remains efficient, economical and effective. Clinicians should prudently consider effective PI application, and we thank Koerner and Grzybowski for encouraging debate and raising the profile of this issue.

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.

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.

EXOGENOUS MENINGOCOCCAL ENDOPHTHALMITIS: A CASE REVIEW.

PURPOSE: We describe a rare case of exogenous endophthalmitis due to Neisseria meningitidis, of which only two have previously been published. METHODS: Retrospective audit of patient's medical notes. PATIENTS: An 82-year-old man from The Royal Victoria Eye and Ear Hospital, a tertiary ophthalmic service in Melbourne, Australia. RESULTS: Found to have exogenous endophthalmitis from a leaking, filtering bleb. CONCLUSION: This seems to be the first case in which a conjunctival swab was diagnostic. These cases demonstrate that it is reasonable to consider meningococcal endophthalmitis in systemically well patients with leaky filtering blebs. Of note for occupational health and safety, prophylaxis is not required for staff contacts treating these patients.

Secondary and Exploratory Outcomes of the Subthreshold Nanosecond Laser Intervention Randomized Trial in Age-Related Macular Degeneration: A LEAD Study Report.

PURPOSE: To evaluate the secondary and exploratory outcomes of the Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study, a 36-month trial of a subthreshold nanosecond laser (SNL) treatment for slowing the progression to late age-related macular degeneration (AMD) in its early stages. DESIGN: Multicenter, randomized, sham-controlled trial. PARTICIPANTS: Two-hundred ninety-two patients with bilateral large drusen. METHODS: Participants were randomly assigned to receive SNL or sham treatment to the study eye at 6-month intervals. MAIN OUTCOME MEASURES: The secondary outcome measure of the LEAD study was the time to development of late AMD, defined by multimodal imaging in the non-study eye. The exploratory outcome measures were the rate of change in best-corrected visual acuity (BCVA), low-luminance visual acuity, microperimetric mean sensitivity, drusen volume in the study and non-study eyes, and participant-reported outcomes based on the Night Vision Questionnaire and Impact of Vision Impairment questionnaire. RESULTS: Progression to late AMD in the non-study eye was not significantly delayed with SNL treatment (hazard ratio, 0.83; 95% confidence interval, 0.40-1.71; P = 0.611). There was no evidence of effect modification based on the coexistence of reticular pseudodrusen; interaction P = 0.065). There was no significant difference between study groups in the rate of change of low-luminance visual acuity, microperimetric mean sensitivity, and drusen volume in the study or non-study eyes, and Night Vision Questionnaire and Impact of Vision Impairment questionnaire scores (all P ≥ 0.167). The rate of BCVA decline was slightly higher for participants in the SNL group compared with the sham treatment group in the study eye (-0.54 and 0.23 letters/year, respectively; P < 0.001) but not the non-study eye (-0.48 and -0.56 letters/year, respectively; P = 0.628). CONCLUSIONS: Subthreshold nanosecond laser treatment of one eye did not have an effect on delaying progression to late AMD in the fellow eye and did not, in general, have an impact on the exploratory structural, functional, and participant-reported outcomes.

Transnational review of visual standards for driving: How Australia compares with the rest of the world.

IMPORTANCE: Driving is a highly visual task and a primary mode of transportation for many people around the world. BACKGROUND: There appears to be little uniformity of vision standards across the world for driving. We reviewed the basic screening visual requirements for obtaining standard private and commercial driving licences for a total of 70 jurisdictions, and reviewed the evidence behind these standards. DESIGN: Systematic review of basic screening vision standards worldwide for driving and literature review. SAMPLES: Published online documentation on visual acuity and field requirements for driving. METHODS: Journal articles, government reports and websites obtained via a Google search were used to review the regulations for driving. This was limited by the comprehensiveness of resources, and countries were excluded if the requirements were unclear or unattainable. A literature review was performed using Medline with keywords vision, driving and visual field. MAIN OUTCOME MEASURES: Visual parameters used for driving assessment. RESULTS: The results suggest significant variations across the world. The visual acuity requirements for a private licence range from a minimum of 6/9 to 6/60. The minimum binocular horizontal field requirement ranges from 110° to 150°. In general, standards for a commercial licence are stricter compared to a private licence. A literature review could not support the current driving standards as evidence-based. CONCLUSIONS AND RELEVANCE: The disunity of driving vision requirements worldwide likely reflects the inconclusive evidence base. Accounting for individual differences and the ability to predict individual risk is important in the context of determining driving licensure.

Prospective randomised clinical trial of intravitreal bevacizumab versus triamcinolone in eyes with diabetic macular oedema undergoing cataract surgery: 6-month results.

AIM: To report the 6-month results of a clinical trial that compared intravitreous bevacizumab (BVB) 1.25 mg versus triamcinolone acetonide (TA) 4 mg when administered as an adjunct during cataract surgery to patients with diabetic macular oedema (DMO). METHODS: Prospective, double-masked, single-centre (Royal Victorian Eye and Ear Hospital, Melbourne) clinical trial. Patients with visually significant cataract and centre-involving DMO (either current or prior) were randomised (1: 1) to receive either intravitreous BVB 1.25 mg or TA 4 mg at the time of cataract surgery and if required at review. Main outcome measures were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline to the 6-month time point of this 12-month study. RESULTS: 61 eyes of 58 patients were enrolled. At baseline, both groups were similar in terms of BCVA and CMT (p>0.2). At 6 months, there was no significant difference in vision between the groups, with mean letter gain of +21.4 (95% CI +14.5 to +28.4) in the TA group and +17.3 (95% CI +12.1 to +22.6) in the BVB group (p=0.35). The TA group had a significant sustained anatomical improvement at 6 months, with a reduction in CMT (-51.4 µm; 95% CI -98.2 to -4.7) compared with thickening in the BVB group (+15.6 µm; 95% CI -26.4 to +57.7, p=0.04). CONCLUSIONS: When given as an adjunct to cataract surgery, both TA and BVB improved visual outcomes at 6 months postoperatively. However, only TA resulted in sustained improvement in CMT, with the majority not requiring any further treatment postoperatively.

The effect of diluting povidone-iodine on bacterial growth associated with speech.

BACKGROUND: Povidone-Iodine (PI) may be diluted when used as an antiseptic prior to an intravitreal injection in an attempt to decrease patient discomfort. This study aims to investigate the effect of diluting povidone-iodine (PI) on bacterial growth from bacterial droplet dispersal associated with speech. METHODS: Participants read a standardised script for 5 min over a blood agar plate positioned at 20 cm in a simulated position of an intravitreal injection procedure. The blood agar plates were subject to a randomised pre-application of 1% PI; 2.5% PI; 5% PI and no pre-application (control). The plates were incubated at 37 °C for 72 h and the number of Colony Forming Units (CFUs) was determined. CFUs were summarised as median and interquartile range (IQR). Wilcoxon rank sum test was used to assess pairwise comparisons of the various PI concentrations to the control group. Any trend across PI concentration was assessed using Kendall's tau rank correlation. RESULTS: Twenty-one subjects participated. Control plates had a median growth of 25 CFUs (interquartile range [IQR]:15-40), 1% PI plates had a median growth of 30 CFUs (IQR:15-82), 2.5% PI had a median growth of 18 CFUs (IQR:10-32) and 5% PI had a median growth of 2 CFUs (IQR:0-5). There was significantly less bacterial growth with 5% PI compared to control (P < 0.001). Bacterial growth at 2.5% PI and 1% PI did not differ significantly from control. There was a statistically significant trend for decreasing colony count as PI concentration increased (P < 0.001). CONCLUSIONS: PI concentrations less than 5% are not effective at reducing bacterial growth from bacterial droplet dispersal associated with speech. When using PI for pre-injection antisepsis, concentrations below 5% should be avoided.

Experiences and perceptions of patients undergoing treatment and quality of life impact of diabetic macular edema: a systematic review.

Diabetic macular edema (DME) is a common cause of visual impairment. Current treatments for DME include laser photocoagulation, corticosteroids and Vascular Endothelial Growth Factor (VEGF) antagonists, which are administered via intravitreal injection. The purpose of this systematic review is to explore the experiences and perceptions of patients undergoing laser, corticosteroid implants and intravitreal injection treatment for DME and the impact on Quality of Life (QoL). A systematic search of the Embase, Medline, PsycINFO and Cinahl electronic databases was conducted to identify all studies with an unlimited date range, published in the English language, full text and incorporating human participants. Hand searching identified two articles. Following the application of the Critical Appraisal Skills Programme (CASP) Quantitative and Qualitative Research Checklist 21 articles were selected for inclusion, as they were deemed pertinent for the purpose of this review. Limited studies have examined DME patients' experiences and perceptions of treatment and QoL. The outcomes of these studies lack agreement on the effectiveness of treatment, treatment preferences and impact of QoL in patients with DME. Future research which enhances current knowledge will therefore serve to improve treatment outcomes and QoL in these patients.

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.

Predictors of visual outcome and the role of early vitrectomy in streptococcal endophthalmitis.

IMPORTANCE: Streptococcal endophthalmitis has devastating sequelae. This study aims to identify factors which may be targeted to optimize patient outcomes. BACKGROUND: This study investigated characteristics influencing visual outcomes and the role of early vitrectomy. DESIGN: Retrospective observational case series of consecutive patients was conducted. PARTICIPANTS: All patients with a culture-positive diagnosis of streptococcal endophthalmitis treated at a tertiary ophthalmology referral centre between July 1997 and February 2012 were included. METHODS: Patient records were reviewed and data collected on their presentation, examination, microbiology results, procedures and final outcome. MAIN OUTCOME MEASURES: Visual acuity (VA) and enucleation/evisceration were measured. RESULTS: Of the 101 patients, 35.6% presented with a VA of hand movements and 42.6% with light perception (LP). Final VA was poor (6/60 or worse) in 77.6% and 24.7% were enucleated/eviscerated. Presenting VA of LP or worse (P = 0.008), no view of fundus (P = 0.001), large number of organisms (P < 0.001), recognition of Streptococcus on Gram stain (P = 0.010), heavy growth on culture (P < 0.001) and more intravitreal injections (P = 0.038) were significantly associated with poor visual outcome (6/60 or worse). Presenting VA of LP or worse (P = 0.042) and non-viridans Streptococcus species (P = 0.002) were significantly associated with enucleation/evisceration. Fifteen patients (14.9%) had early vitrectomy within 48 h which was not associated with poor final VA or removal of the eye (P = 1.000). CONCLUSIONS AND RELEVANCE: Early vitrectomy did not influence visual outcome in this cohort. Microbiology results were useful in predicting poor outcomes, and may allow clinicians to make early treatment decisions and provide prognostic information for patients.