lncRNA H19 prevents endothelial-mesenchymal transition in diabetic retinopathy.

AIMS/HYPOTHESIS: The pathophysiology of diabetic retinopathy is linked to hyperglycaemia and its effect on retinal microvascular tissues. The resulting endothelial injury changes the endothelial cell phenotype to acquire mesenchymal properties (i.e. endothelial-mesenchymal transition [EndMT]). Such changes can be regulated by epigenetic mechanisms, including long non-coding RNAs (lncRNAs). lncRNA H19 may influence EndMT through TGF-ß. We investigated the role of H19 in regulating EndMT during diabetic retinopathy. METHODS: H19 was overexpressed or silenced in human retinal endothelial cells exposed to various glucose levels. The cells were examined for H19, endothelial and mesenchymal markers. We then expanded the study to retinal tissues in a mouse model of diabetic retinopathy and also examined vitreous humour samples from individuals with proliferative diabetic retinopathy. RESULTS: Expression of H19 was downregulated in high glucose conditions (25 mmol/l). H19 overexpression prevented glucose-induced EndMT. Such changes appear to involve TGF-ß through a Smad-independent mechanism. Diabetes caused downregulation of retinal H19. Using H19 knockout mice, we demonstrated similar EndMT in the retina. Examination of vitreous humour from individuals with proliferative diabetic retinopathy also reinforced the downregulation of H19 in diabetes. CONCLUSIONS/INTERPRETATION: We therefore concluded that H19 regulates EndMT in diabetic retinopathy through specific mechanisms. DATA AVAILABILITY: The results from our previous microarray can be found online using the GEO accession number GSE122189.

Effectiveness of Nonmydriatic Ultra-Widefield Retinal Imaging to Screen for Diabetic Eye Disease: A Randomized Controlled Trial (Clearsight).

OBJECTIVE: Suboptimal diabetic eye disease screening is a major cause of preventable vision loss. Screening barriers include mydriasis and the need for dedicated screening appointments. The Clearsight trial assessed whether nonmydriatic ultra-widefield (NM UWF) screening on the day of a diabetes clinic visit improved detection of clinically important eye disease versus usual screening. RESEARCH DESIGN AND METHODS: This single-center, randomized, parallel-group controlled trial was conducted at St. Joseph's Health Care, London, Ontario, Canada. Adults with diabetes due for screening were randomized to same-day, on-site screening (NM UWF imaging) on the day of a scheduled diabetes clinic visit or usual screening (encouraged to arrange optometrist screening). The primary outcome was detection of actionable eye disease (AED), defined as the need for an ophthalmology referral or increased ocular surveillance. The primary analysis (modified intention-to-screen) compared the proportions of AED between groups within 1 year of enrollment. RESULTS: Of 740 participants randomized between 7 March 2016 and 17 April 2019, 335 on-site screening and 323 usual screening participants met criteria for the primary analysis. More AED was detected in the on-site screening group than in the usual screening group (50 of 335 [14.9%] vs. 22 of 323 [6.8%]; adjusted odds ratio 2.51; 95% CI 1.49-4.36). The number needed to screen by on-site screening in order to detect 1 additional patient with AED was 13 (95% CI 8-29). CONCLUSIONS: Same-day, on-site screening by NM UWF imaging increased the detection of clinically important diabetic eye disease versus usual screening. Integration of NM UWF imaging into routine diabetes clinic visits improved screening adherence and has the potential to prevent vision loss.

Expressions of Serum lncRNAs in Diabetic Retinopathy - A Potential Diagnostic Tool.

With increasing incidence of diabetes worldwide, there is an ever-expanding number of patients with chronic diabetic complications such as diabetic retinopathy (DR), one of the leading causes of blindness in the working age population. Early screening for the onset and severity of DR is essential for timely intervention. With recent advancements in genomic technologies, epigenetic alterations in DR are beginning to unravel. Long non-coding RNAs (lncRNAs), which are key epigenetic mediators, have demonstrated implications in several (DR) related processes. Based on the previous research, we have developed a serum-based, multi-panel PCR test using 9 lncRNAs (ANRIL, MALAT1, WISPER, ZFAS1, H19, HOTAIR, HULC, MEG3, and MIAT) to identify and validate whether this panel could be used as a diagnostic and prognostic tool for DR. We initially used a cell culture model (human retinal endothelial cells) and confirmed that 25 mM glucose induces upregulations of ANRIL, HOTAIR, HULC, MALAT1, and ZFAS1, and downregulation of H19 compared to 5 mM glucose controls. Then as an initial proof-of-concept, we tested vitreous humor and serum samples from a small cohort of non-diabetic (N=10) and diabetic patients with proliferative retinopathy (PDR, N=11) and measured the levels of the 9 lncRNAs. Differential expressions of lncRNAs were found in the vitreous and serum of patients and showed significant correlations. We expanded our approach and assessed the same lncRNAs using samples from a larger cohort of diabetic (n= 59; M/F:44/15) and non-diabetic patients (n= 11; M/F:4/7). Significant increased lncRNA expressions of ANRIL, H19, HOTAIR, HULC, MIAT, WISPER and ZFAS1 were observed in the serum of diabetic patients (with varying stages of DR) compared to non-diabetics. No significant correlations were demonstrated between lncRNA expressions and creatinine or glycated hemoglobin (HbA1C) levels. Using ROC and further analyses, we identified distinct lncRNA phenotype combinations, which may be used to identify patients with DR. Data from this study indicate that a panel of serum lncRNAs may be used for a potential screening test for DR. Further large-scale studies are needed to validate this notion.

Long-term benefit of sustained-delivery fluocinolone acetonide vitreous inserts for diabetic macular edema.

OBJECTIVE: To assess the efficacy and safety of intravitreal inserts releasing 0.2 µg/day (low dose) or 0.5 µg/day (high dose) fluocinolone acetonide (FA) in patients with diabetic macular edema (DME). DESIGN: Two parallel, prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trials. PARTICIPANTS: Subjects with persistent DME despite at least 1 macular laser treatment were randomized 1:2:2 to sham injection (n = 185), low-dose insert (n = 375), or high-dose insert (n = 393). METHODS: Subjects received study drug or sham injection at baseline and after 6 weeks were eligible for rescue laser. Based on retreatment criteria, additional study drug or sham injections could be given after 1 year. MAIN OUTCOME MEASURES: The primary outcome was the percentage of patients with improvement from baseline best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Trial (ETDRS) letter score of 15 or more at month 24. Secondary outcomes included other parameters of visual function and foveal thickness (FTH). RESULTS: The percentage of patients with improvement from baseline ETDRS letter score of 15 or more at month 24 was 28.7 and 28.6 in the low- and high-dose insert groups, respectively, compared with 16.2 in the sham group (P = 0.002 for each). Benefit occurred for both doses compared with sham at 3 weeks and all subsequent time points. The mean improvement in BCVA letter score between baseline and month 24 was 4.4 and 5.4 in the low- and high-dose groups, respectively, compared with 1.7 in the sham group (P = 0.02 and P = 0.016). At all time points compared with sham, there was significantly more improvement in FTH. Subjects requiring cataract surgery were more frequent in the insert groups, and their visual benefit was similar to that of subjects who were pseudophakic at baseline. Glaucoma requiring incisional surgery occurred in 3.7%, 7.6%, and 0.5% of the low-dose, high-dose, and sham groups, respectively. CONCLUSIONS: Both low- and high-dose FA inserts significantly improved BCVA in patients with DME over 2 years, and the risk-to-benefit ratio was superior for the low-dose insert. This is the first pharmacologic treatment that can be administered by an outpatient injection to provide substantial benefit in patients with DME for at least 2 years.

The Long Non-Coding RNA HOTAIR Is a Critical Epigenetic Mediator of Angiogenesis in Diabetic Retinopathy.

Purpose: Diabetic retinopathy (DR) remains a pressing issue worldwide. Abnormal angiogenesis is a distinct vascular lesion in DR, and research has established that vascular endothelial growth factor A (VEGF-A) is a primary mediator of such changes. However, limitations in current anti-VEGF therapies suggest that our understanding of molecular networks underlying ocular angiogenesis remains far from complete. Based on our long non-coding RNA (lncRNA) array analyses, HOX antisense intergenic RNA (HOTAIR) was identified as one of the top upregulated lncRNAs in high glucose-cultured human retinal endothelial cells (HRECs). Given the well-documented roles of HOTAIR in cancer, no studies have examined the epigenetic implications of HOTAIR in DR, and we investigated such relationships herein. Methods: We used HRECs exposed to various glucose concentrations and epigenetic modulators to examine HOTAIR, angiogenic, and DR-related molecular markers. Oxidative stress, angiogenesis, and mitochondrial dysfunction were assessed. Retinal tissues of diabetic rodents and the vitreous humor and serum of patients with proliferative DR were also investigated. Results: Hyperglycemia significantly augmented HOTAIR expression in HRECs and promoted angiogenesis, oxidative damage, and mitochondrial aberrations. Similarly, vitreous humor and serum from proliferative DR patients and retinas from diabetic animals demonstrated increased HOTAIR expression compared to non-diabetic controls. HOTAIR knockdown protected against glucose-induced increases of angiogenic and diabetes-associated molecules in the retina. Mechanistically, we showed that HOTAIR exerts its capabilities by preventing oxidative stress and modulating epigenetic pathways involving histone methylation, histone acetylation, DNA methylation, and transcription factors. Conclusions: Our findings suggest that HOTAIR is a critical lncRNA in the pathogenesis of DR and may potentially be important for diagnostic and therapeutic targeting.

Two-year analysis of changes in the optic nerve and retina following anti-VEGF treatments in diabetic macular edema patients.

Purpose: To evaluate long-term structural and functional changes that happen to the optic nerve and retina following ranibizumab (Lucentis) injections in diabetic macular edema (DME) patients. Methods: Patients with clinically significant DME requiring anti-VEGF injections underwent pre-injection baseline, 6, 12, and 24 month follow-up tests. The tests performed were optical coherence tomography (OCT), best-corrected visual acuity (BCVA), and visual field (VF). Wide-field fluorescein angiogram (IVFA) was performed to monitor the progression of diabetic ischemia. Results: A total of 30 patients requiring anti-VEGF injections and 21 control patients not requiring anti-VEGF injections were enrolled in the study. From baseline, the average macular thickness significantly decreased (p<0.0002) over the 24-month time period. Mean perfused ratio significantly increased (p<0.0005) at 6, 12, and 24 months. Cup volume and vertical cup-to-disk ratio significantly increased (p<0.0014) over the study period. This was verified by masked independent grading of patient optic nerve stereo-photographs by glaucoma specialists. BCVA significantly (p<0.0006) improved over the study period. VFs showed a non-significant trend of deteriorating peripheral vision at 12 and 24 months. Conclusion: Clinically, anti-VEGF therapy appears to affect the optic nerve by increasing cup volume and increasing vertical cup/disk ratio over time. The results provide a cautionary note to monitor both the retina and optic nerve status in patients undergoing frequent injections.

Prospective evaluation of aflibercept in pigment epithelial detachments secondary to neovascular age related macular degeneration.

OBJECTIVE: To assess the efficacy of intravitreal aflibercept in treating visual loss and structural changes in patients with pigment epithelial detachments (PED) secondary to neovascular age-related macular degeneration (nAMD). METHODS: Prospective, exploratory, open-label study (ClinicalTrials.gov Identifier: NCT02142296). Participants with PED secondary to nAMD were enrolled and received intravitreal aflibercept injection on a monthly basis for 3 months, followed by injections on a bimonthly basis for another 9 months. Best-corrected visual acuity (BCVA), ophthalmic examinations, optical coherence tomography (OCT) imaging, and fluorescein angiography were performed based on a predetermined schedule. RESULTS: Thirty-six participants (37 eyes) were enrolled. At the end of study, 74.3% eyes demonstrated PED height reduction of 25% or more and 34.3% demonstrated complete resolution. The average reduction in retinal thickness was 128.4 µm. Participant eyes who had at least a 25% reduction in PED height at month 4 were labelled as "responders" (73.0%, n = 27), and those who had less than 25% reduction in PED height were labelled as "partial-responders" (27.0%, n = 10). Responders demonstrated more significant reduction in PED height than partial-responders (p <0.0001). The average gain in BCVA was 10.1 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Responders demonstrated more gain in BCVA than partial-responders (p = 0.0018). Among the responders, 57.7% demonstrated disease recurrences with increase in PED height during bimonthly dosing. CONCLUSIONS: Intravitreal aflibercept injection for patients with PEDs secondary to nAMD has high response rate with few adverse events. Responders demonstrated BCVA gains, as well as structural improvements. However, high recurrence rate was found on bimonthly maintenance dosing.

MALAT1: An Epigenetic Regulator of Inflammation in Diabetic Retinopathy.

Despite possessing limited protein-coding potential, long non-coding RNAs (lncRNAs) have been implicated in a myriad of pathologic conditions. Most well documented in cancer, one prominent intergenic lncRNA known as MALAT1 is notorious for its role in impacting epigenetic mechanisms. In this study, we established a novel epigenetic paradigm for MALAT in diabetic retinopathy (DR) by employing siRNA-mediated MALAT1 knockdown in human retinal endothelial cells (HRECs), a Malat1 knockout animal model, vitreous humor from diabetic patients, pharmacological inhibitors for histone and DNA methylation, RNA immunoprecipitation, western blotting, and a unique DNA methylation array to determine glucose-related alterations in MALAT1. Our findings indicated that MALAT1 is capable of impacting the expressions of inflammatory transcripts through its association with components of the PRC2 complex in diabetes. Furthermore, the vitreous humors from diabetic patients revealed increased expressions of MALAT1, TNF-α, and IL-6. Intriguingly, our DNA methylation array demonstrated that transient high glucose exposure in HRECs does not contribute to significant methylation alterations at CpG sites across the MALAT1 gene. However, global inhibition of DNA methyltransferases induced significant increases in MALAT1 and associated inflammatory transcripts in HRECs. Our findings collectively demonstrate the importance of MALAT1 in inflammation and epigenetic regulation in DR.

Comparison of in vitro toxicity of single vs double exposures of indocyanine green in human retinal pigment epithelial cell cultures.

PURPOSE: To compare the in vitro effect of a single brief indocyanine green (ICG) exposure with a double exposure on retinal pigment epithelial (RPE) cells. DESIGN: In vitro laboratory experimental study. METHODS: Human ARPE-19 cells were exposed to a single dilute ICG exposure (0.5 mg/ml) or to two sequential exposures of identical volume and concentration. Viability was measured with a mitochondrial dehydrogenase assay and compared with nonexposed control cells. RESULTS: Cell viability was not statistically different between the single-exposed, double-exposed, or control cell populations. CONCLUSIONS: When used intraoperatively to stain the internal limiting membrane, dilute ICG dye sometimes does not adequately enhance visualization of the internal limiting membrane. Occasionally, it is necessary to repeat the dye exposure to achieve the desired visibility. In this study, RPE cells subjected to two consecutive short exposures of ICG showed no marked difference in cell survival when compared with cells exposed to a single application of ICG and to control cells.

A randomised trial of non-mydriatic ultra-wide field retinal imaging versus usual care to screen for diabetic eye disease: rationale and protocol for the Clearsight trial.

INTRODUCTION: Suboptimal screening for diabetic eye disease is a major cause of preventable vision loss. Screening barriers include mydriasis and the extra time patients need to attend dedicated eye screening appointments. In the Clearsight trial, we are testing whether screening by non-mydriatic ultra-wide field (NM UWF) imaging on the day patients attend their diabetes outpatient clinic visit improves detection of clinically important eye disease compared with usual screening. METHODS AND ANALYSIS: Patients with diabetes due for a screening eye exam by the 2013 Canadian Diabetes Association (CDA) practice guidelines are being randomised to on-site screening by NM UWF imaging on the day of their clinic visit or to usual screening where, per CDA guidelines, they are encouraged to arrange an exam by an optometrist. The primary outcome is actionable eye disease (AED) based on a need for referral to ophthalmology and/or increased ocular surveillance. The primary analysis will use an intention-to-screen approach that compares the proportions of detected AED between on-site and usual screening groups under a superiority hypothesis in favour of on-site screening. With 740 randomised participants, the study will have 80% power to detect ≥5% absolute increase in the AED rate among on-site screening versus usual screening participants. This difference translates into a number-needed-to-screen by on-site screening of 20 to detect 1 additional person with AED. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review board of Western University. The findings of the trial will be disseminated directly to participants and through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ClinicalTrials.Gov NCT02579837 (registered 16 October 2015). PROTOCOL ISSUE DATE: 18 November 2015.

Endothelins: regulators of extracellular matrix protein production in diabetes.

Fibronectin (FN), a key extracellular matrix protein, is upregulated in target organs of diabetic angiopathy and in cultured cells exposed to high levels of glucose. FN has also been reported to undergo alternative splicing to produce the extra domain-B (ED-B) containing isoform, which is exclusively expressed during embryogenesis, tissue repair, and tumoral angiogenesis. The present study was aimed at elucidating the role and mechanism of endothelins (ETs) in FN and ED-B FN expression in diabetes. We investigated vitreous samples for ED-B FN expression from patients undergoing vitrectomy for proliferative diabetic retinopathy. Our results show increased FN and ED-B FN expression in the vitreous of diabetic patients in association with augmented ET-1. Using an antibody specific to the ED-B segment of FN, we show an increase in serum ED-B FN levels in patients with diabetic retinopathy and nephropathy. We further examined retinal tissues, as well as renal and cardiac tissues, from streptozotocin-induced diabetic rats. Diabetes increased FN and ED-B FN in all three organs, which was prevented by ET antagonist bosentan. To provide insight into the mechanism of glucose-induced and ET-mediated ED-B FN upregulation, we assayed endothelial cells (ECs). Inhibition of mitogen-activated protein kinase with pharmacological inhibitors and protein kinase B with dominant negative transfections prevented glucose- and ET-1-mediated FN and ED-B FN expression. Furthermore, treatment of cells exposed to high levels of glucose with ET antagonist prevented the activation of all signaling pathways studied and normalized glucose-induced ED-B FN expression. We then determined the functional significance of ED-B in ECs and show that ED-B FN is involved in vascular endothelial growth factor expression and cellular proliferation. These studies show that glucose-induced and ET-mediated FN and ED-B FN expressions involve complex interplays between signaling pathways and that ET may represent an ideal target for therapy in chronic diabetic complications.

A case of unilateral and spontaneously resolving posterior uveitis with overlapping features of Vogt-Koyanagi-Harada disease and Acute Posterior Multifocal Placoid Pigment Epitheliopathy.

INTRODUCTION: VKH disease is a chronic, bilateral, granulomatous panuveitis with potential involvement of neurological, auditory and integumentary systems. On the other hand, APMPPE is believed to be an immune-driven chorioretinal vascular disease characterized by multifocal, flat, grey-white placoid lesions at the level of the RPE. We describe a case with overlapping figures of both conditions. CASE DESCRIPTION: A 19-year-old female presented with unilateral blurry vision and was found to have clinical and IVFA findings consistent with APMPPE. Her OCT study demonstrated typical VKH findings with large areas of serous neurosensory retinal detachment and intra-retinal cystoid spaces with enclosed membranous structures. She was closely followed but was not treated with high dose corticosteroid. Spontaneous and complete resolution of her symptoms and clinical, IVFA and OCT findings were achieved by day 25. DISCUSSION: This is the first reported case of spontaneously resolving, unilateral VKH disease in the absence of high dose corticosteroid treatment with overlapping features of APMPPE. CONCLUSIONS: The imaging and clinical findings of both VKH disease and APMPPE raise the notion that VKH disease and APMPPE could be an overlapping spectrum of inflammatory processes, rather than distinct disease entities.

Oncofetal fibronectin in diabetic retinopathy.

PURPOSE: Imbalance between extracellular matrix protein synthesis and degradation is a key feature of diabetic retinopathy. Fibronectin, a predominant constituent of the extracellular matrix, has been shown to undergo alternative splicing to produce embryonic isoforms in various pathologic conditions, such as fibrotic diseases and tumorigenesis. Two such isoforms, oncofetal fibronectin variants that are characterized by the inclusion of the oncofetal domains A and B, were the focus of the present study. METHODS: The expression of oncofetal fibronectin variants was determined in human vitreous samples obtained from patients undergoing vitrectomy for proliferative diabetic retinopathy and nondiabetes-associated ocular conditions such as macular hole. In addition, an animal model of chronic diabetes and cultured endothelial cells was used to elucidate the mechanistic basis for this aberrant expression of oncofetal fibronectin. RESULTS: Expression of fibronectin containing the oncofetal domain B was upregulated in the vitreous of patients with diabetic retinopathy. CONCLUSIONS: Use of a well-established animal model of chronic diabetic complications and cultured endothelial cells showed that diabetes-induced upregulation of oncofetal fibronectin is, in part, dependent on hyperglycemia-induced transforming growth factor-beta1 and endothelin-1. Furthermore, the data suggest that oncofetal fibronectin is involved in endothelial cell proliferation.

Comparison of the in vitro toxicity of indocyanine green to that of trypan blue in human retinal pigment epithelium cell cultures.

PURPOSE: To compare the in vitro toxicity of indocyanine green (ICG) to that of trypan blue (TB) in human retinal pigment epithelium cell cultures. The use of ICG and TB in macular hole surgery is discussed. DESIGN: In vitro cell biology experimental study. METHODS: The ICG dye and TB were applied to ARPE-19, a commercially available human retinal pigment epithelium cell line. Cultures were established and maintained according to supplier protocols. The ICG dye, TB or Hank's balanced salt solution (controls) were then applied to the cells at varying concentrations and over various exposure periods. Fiberoptic light was also applied to cells to assess for the possibility of a potentiating phototoxic effect. Cell viability fractions were determined using a well-studied mitochondrial dehydrogenase assay. RESULTS: The TB was not toxic to the retinal pigment epithelium cell cultures at any concentration or over any period of exposure, whereas ICG dye demonstrated dose-dependent and exposure-dependent toxicity. The ICG dye was found to be toxic to the cells at all tested concentrations between 5.0 mg/ml (stock concentration, 26.1% cell survival) and 0.5 mg/ml (92.8% cell survival) over a 3-minute exposure. No toxicity to TB was seen at the stock concentration of 1.5 mg/mL. Addition of light to the cultures did not significantly alter cell viability with either dye. Long periods of exposure, 2 hours, 24 hours, and 72 hours, to minute concentrations of either dye did not produce significant cell death. CONCLUSIONS: Indocyanine green demonstrates more toxicity than TB to human retinal pigment epithelium cell cultures. This is independent of any phototoxic potentiating effect of fiberoptic light or solvent toxicity. A clinically useful concentration of 0.5-mg/ml ICG causes low cytotoxicity at 3 minutes' exposure (cell survival 92.8%) and shows no detectable toxicity at 1-minute exposure (cell survival 102%).

Costs and Quality of Life in Diabetic Macular Edema: Canadian Burden of Diabetic Macular Edema Observational Study (C-REALITY).

Purpose. To characterize the economic and quality of life burden of diabetic macular edema (DME) in Canadian patients. Patients and Methods. 145 patients with DME were followed for 6 months with monthly telephone interviews and medical chart reviews at months 0, 3, and 6. Visual acuity in the worst-seeing eye was assessed at months 0 and 6. DME-related healthcare costs were determined over 6 months, and vision-related (National Eye Institute Visual Functioning Questionnaire) and generic (EQ-5D) quality of life was assessed at months 0, 3, and 6. Results. Mean age of patients was 63.7 years: 52% were male and 72% had bilateral DME. At baseline, visual acuity was categorized as normal/mild loss for 63.4% of patients, moderate loss for 10.4%, and severe loss/nearly blind for 26.2%. Mean 6-month DME-related costs/patient were as follows: all patients (n = 135), $2,092; normal/mild loss (n = 88), $1,776; moderate loss (n = 13), $1,845; and severe loss/nearly blind (n = 34), $3,007. Composite scores for vision-related quality of life declined with increasing visual acuity loss; generic quality of life scores were highest for moderate loss and lowest for severe loss/nearly blind. Conclusions. DME-related costs in the Canadian healthcare system are substantial. Costs increased and vision-related quality of life declined with increasing visual acuity severity.

Patient preferences in the treatment of diabetic retinopathy.

OBJECTIVE: Accounting for patient preferences may be especially important in diabetes mellitus, given the challenge in identifying factors associated with treatment adherence. Although preference studies have been performed in diabetes, none have examined treatments used in diabetic retinopathy (DR). The objective of this study was to elicit patient preferences for attributes associated with antivascular endothelial growth factor, focal and panretinal laser, and steroid therapy used in DR management. METHODS: A cross-sectional conjoint survey was administered to DR patients at three Canadian eye centers. The survey involved making tradeoffs among 11 DR treatment attributes, including the chance of improving vision and risks of adverse events over a 1-year treatment period. Attribute utilities were summed for each product profile to determine the most preferred treatment. RESULTS: Based on the results from 161 patients, attributes affecting visual functioning, including improving visual acuity and reducing adverse events (eg, chance of cataracts), were more important than those not directly affecting vision (eg, administration). Overall, 52%, 20%, 17%, and 11% preferred the product profiles matching to the antivascular endothelial growth factor, steroid, focal laser, and panretinal laser therapies. Preferences did not vary substantially by previous treatment experience, age, or type of DR (macular edema, proliferative DR, both or neither), with the exception that more macular edema only patients preferred focal laser over steroid treatment (19% versus 14%, respectively). CONCLUSIONS: When considering the potential effects of treatment over a 1-year period, treatment preferences in DR are most influenced by those that may positively or negatively affect visual functioning.

Immediately sequential bilateral cataract surgery versus delayed sequential bilateral cataract surgery: potential hospital cost savings.

OBJECTIVE: Cataract surgery represents a substantial cost to health care systems around the world. Canada's socialized medical system allows an opportunity to accurately track costing because of the institutional record keeping necessary for public reporting to provincial governments. Cataract surgical costs consist of medical costs, hospital costs, and social costs. Our study compared the hospital costs of immediately sequential bilateral cataract surgery (ISBCS) with delayed sequential bilateral cataract surgeries (DSBCS), minimizing other interfering variables. DESIGN: Retrospective chart review with collection of associated costing information from the hospital. PARTICIPANTS: Twenty-two consecutive patients undergoing ISBCS with posterior chamber intraocular lens implantation and a randomly selected group of 22 patients undergoing similar DSBCS during the same period. METHODS: Hospital costs were determined using the London Health Sciences Centre case-costing system. Average costs were calculated and compared statistically. RESULTS: Average hospital costs were significantly reduced when performing ISBCS (p < 0.0001); 2 separate unilateral cataract surgeries totaled $1566.30, compared with $1059.10 for one bilateral cataract surgery (32.4% reduction). Pre- and post-operative in-hospital care accounted for a significant portion of this difference (54%), as 2 separate surgeries cost $547.92 compared with $273.96 for ISBCS. CONCLUSIONS: ISBCS provided considerable hospital cost savings compared to DSBCS.

Patient preferences for diabetic retinopathy health States.

PURPOSE. To develop standardized descriptions of health states that characterize vision-specific functional impacts of diabetic retinopathy (DR) according to levels of visual acuity and contrast sensitivity and to elicit preferences for these health states from persons with DR and assign weighted values to them. METHODS. Vision-specific descriptions of health states were developed based on a literature review and patient and physician interviews. The content was based on items from the National Eye Institute Visual Functioning Questionnaire (VFQ) and reflected functional impacts experienced by DR patients. Values were assigned to the range of health states, anchored by the extremes full vision and death, by using the time-tradeoff method in a sample of 98 Canadian DR patients from three clinical centers. RESULTS. The mean age of the sample was 60.4 years, and 56% were men. Mean preferences decreased from 0.98 (better-eye logMAR [Snellen equivalent] acuity, > or =20/40; worse-eye Snellen equivalent, > or =20/200) to 0.67 (Snellen equivalent visual acuity, < or =20/200, contrast sensitivity, < or =21 letters bilaterally). Preferences decreased with increasing severity of functional deficits and did not vary significantly by sex, age, VFQ quartile, or better- or worse-eye acuity. CONCLUSIONS. This is the first study that has been conducted to estimate preferences for standardized DR-specific health states, accounting for visual acuity and contrast sensitivity in both eyes. The results showed that the development and progression of DR are associated with substantial declines in preferences. In addition to the progressively greater impact from declining ETDRS visual acuity and contrast sensitivity, preference weights declined with increasing bilateral disparity. These preference values are useful for comparing the cost effectiveness of ophthalmic treatments.