Loss-of-function variants in UBAP1L cause autosomal recessive retinal degeneration.

PURPOSE: Inherited retinal diseases (IRDs) are a group of monogenic conditions that can lead to progressive blindness. Their missing heritability is still considerable, due in part to the presence of disease genes that await molecular identification. The purpose of this work was to identify novel genetic associations with IRDs. METHODS: Patients underwent a comprehensive ophthalmological evaluation using standard-of-care tests, such as detailed retinal imaging (macular optical coherence tomography and short-wavelength fundus autofluorescence) and electrophysiological testing. Exome and genome sequencing, as well as computer-assisted data analysis were used for genotyping and detection of DNA variants. A minigene-driven splicing assay was performed to validate the deleterious effects of 1 of such variants. RESULTS: We identified 8 unrelated families from Hungary, the United States, Israel, and The Netherlands with members presenting with a form of autosomal recessive and nonsyndromic retinal degeneration, predominantly described as rod-cone dystrophy but also including cases of cone/cone-rod dystrophy. Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later. Myopia greater than 5 diopters was present in 5 of 7 cases with available refractive data, and retinal detachment was reported in 2 cases. All ascertained patients carried biallelic loss-of-function variants in UBAP1L (HGNC: 40028), a gene with unknown function and with homologies to UBAP1, encoding a protein involved in ubiquitin metabolism. One of these pathogenic variants, the intronic NM_001163692.2:c.910-7G>A substitution, was identified in 5 unrelated families. Minigene-driven splicing assays in HEK293T cells confirmed that this DNA change is responsible for the creation of a new acceptor splice site, resulting in aberrant splicing. CONCLUSION: We identified UBAP1L as a novel IRD gene. Although its function is currently unknown, UBAP1L is almost exclusively expressed in photoreceptors and the retinal pigment epithelium, hence possibly explaining the link between pathogenic variants in this gene and an ocular phenotype.

Qualitative and quantitative comparison of two semi-manual retinal vascular density analyzing methods on optical coherence tomography angiography images of healthy individuals.

The aim of this study was to evaluate qualitative and quantitative differences in vascular density analysis of an established and a novel alternative for post-processing on optical coherence tomography angiography (OCTA) images in healthy individuals. OCTA examinations of 38 subjects were performed. After extracting the images, two semi-manual post-processing techniques, the already established Mexican hat filtering (MHF) and an alternative, the Shanbhag thresholding (ST) were applied. We assessed Vessel Density (VD), Skeleton Density (SkD) and Vessel Diameter Index (VDI). We analyzed the results in order to establish similarities or potentially relevant differences. Regarding SkD and VD, MHF generally gave higher values than ST. Simultaneously, mean values were also predominantly higher by MHF; however, standard deviations (SD) were higher by ST (range [mean ± SD]: 0.054 ± 0.038 to 0.134 ± 0.01 and 0.134 ± 0.095 to 0.362 ± 0.028 vs 0.012 ± 0.014 to 0.087 ± 0.03 and 0.039 ± 0.047 to 0.4 ± 0.095 for SkD and VD with MHF vs SkD and VD with ST, respectively). Values of VDI were considerably higher with ST than with MHF, while standard deviation was still significantly higher with ST (range [mean ± SD]: 2.459 ± 0.144 to 2.71 ± 0.084 and 2.983 ± 0.929 to 5.19 ± 1.064 for VDI with MHF and ST, respectively). The noise level reduction of the two methods were almost identical (noise levels: 65.8% with MHT and 65.24% with ST). Using MHF, the vascular network gets more fragmented by an average of 40% compared to ST. Both methods allow the segmentation of the vascular network and the examination of vascular density parameters, but they produce largely inconsistent results. To determine if these inconsistent results are clinically meaningful, and which method is more suitable for clinical use, our results provide further evidence that detailed understanding of the image analysis method is essential for reliable decision making for patients with retinal pathology. For longitudinal monitoring, use of the same image processing method is recommended.

First-in-Human Safety Study of Femtosecond Laser Image-Guided Trabeculotomy for Glaucoma Treatment: 24-month Outcomes.

Purpose: Pilot study to evaluate adverse events and intraocular pressure (IOP)-lowering of a novel, noninvasive glaucoma procedure, femtosecond laser, image-guided, high-precision trabeculotomy (FLIGHT). Design: Prospective, nonrandomized, single-center, interventional, single-arm clinical trial. Participants: Eighteen eyes from 12 patients with open-angle glaucoma. Methods: Eighteen eyes from 12 patients underwent FLIGHT, creating a single channel measuring 500-µm wide by 200-µm high through the trabecular meshwork and into Schlemm's canal. Adverse events, IOP, and other parameters were evaluated out to 24 months. Main Outcome Measures: Outcomes were the rates and types of adverse events and the rate of postprocedure best-corrected visual acuity loss (≥ 2 lines) compared with baseline. Efficacy outcomes were reduction in mean intraocular pressure (IOP) with respect to baseline and the percentage of eyes with a ≥ 20% reduction in IOP. Results: Eighteen eyes from 12 patients were enrolled in the study; 11 patients (17 eyes) returned at 24 months. There were no serious adverse events related to the laser treatment. Well-defined channels were clearly visible at 24 months by gonioscopy and anterior segment OCT, with no evidence of closure. At 24 months, the mean IOP was reduced by 34.6% from 22.3 ± 5.5 to 14.5 ± 2.6 mmHg (P < 5e-5), with an average of 2.0 ± 1.2 hypotensive medications compared with 2.2 ± 1.1 at baseline (P = 0.22). Fourteen out of the 17 study eyes (82.3%) achieved a ≥ 20% reduction in IOP at 24 months when compared with baseline. Conclusion: The FLIGHT system demonstrated a favorable safety profile in this initial pilot study, with no device-related serious adverse events. The channels appeared patent at 24 months, indicating medium-term durability. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Ophthalmic Aspects of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Narrative Review.

The aim of our review article was to summarize the current literature on Stevens-Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN). SJS/TEN is a serious, rare multi-system, immune-mediated, mucocutaneous disease with a significant mortality rate that can lead to severe ocular surface sequelae and even to bilateral blindness. Restoration of the ocular surface in acute and chronic SJS/TEN is challenging. There are only limited local or systemic treatment options for SJS/TEN. Early diagnosis, timely amniotic membrane transplantation and aggressive topical management in acute SJS/TEN are necessary to prevent long-term, chronic ocular complications. Although the primary aim of acute care is to save the life of the patient, ophthalmologists should regularly examine patients already in the acute phase, which should also be followed by systematic ophthalmic examination in the chronic phase. Herein, we summarize actual knowledge on the epidemiology, aetiology, pathology, clinical appearance and treatment of SJS/TEN.

Intraocular neutralizing antibodies against aflibercept in patients with age related macular degeneration.

PURPOSE: To detect immunoglobulins in aqueous humour of AMD patients after repeated administration of intravitreal aflibercept. PATIENTS AND METHODS: Twenty-one patients (age: 77.85 ± 9.21 years) previously treated with intravitreal aflibercept due to wet type age-related macular degeneration (AMD group) and 18 age-matched control subjects (age: 69.75 ± 12.67 years) were included in this study. Patients in the AMD group received a mean of 5 intravitreal injections (min: 1 max: 17) prior to the cataract surgery. Samples of aqueous humour (50 µl) were obtained by anterior chamber paracentesis as the first step of routine cataract surgery. The IgG content of the samples was analysed by an in-house developed ELISA system. RESULTS: A significant increase in nonspecific IgG levels in the AMD group was detected compared to the control group (13.37 ± 6.65 vs. 9.44 ± 6.55 µg/ml; p = 0.03). In 11 patients, intraocular anti-aflibercept immunoglobulins could be detected (0.05 ± 0.01 µg/ml) which was significantly higher than the limit of detection for anti-aflibercept (0.04 µg/ml; p = 0.001). No correlation was found between the number of injections or the type of CNV and the aqueous level of anti-aflibercept (r = 0.02; p = 0.95). CONCLUSION: According to our results, penetration of non-specific systemic antibodies through the impaired blood-retinal barrier is higher in patients with neovascular AMD than in subjects with an intact structural barrier. Evaluation of neutralizing antibodies to anti-VEGF agents in the aqueous humour can lead us to understanding tachyphylaxis and changes in intraocular immune mechanisms due to AMD.

Atrophy of retinal vessels in neovascular age-related macular degeneration following long-term treatment with 20 intravitreal anti-VEGF injections.

BACKGROUND: The study aimed to evaluate the changes in retinal vascular density in exudative age-related macular degeneration (AMD) after long-term anti-VEGF treatment using optical coherence tomography angiography (OCT-A), and to compare these changes with the vascular density in AMD treated for one year and healthy eyes. METHODS: In our cross-sectional study OCT-A was performed on 60 eyes of 60 patients. Group AMD 20 × consisted of patients receiving long-term (minimum 20 injections) aflibercept therapy (n = 17), and Group AMD one year consisted of patients treated for one year with a treat & extend protocol (n = 25). The vascular density values obtained with OCT-A were compared with an age-matched control group of 18 healthy eyes. We examined the central retinal thickness (CRT), the vascular density of the fovea and parafovea in the superficial and deep retinal plexus, and evaluated the extent of the non-flow area and the foveal avascular zone (FAZ) on a 3 × 3 mm macular region. Kruskal-Wallis test was performed for statistical analysis. RESULTS: In Group AMD 20x, the vascular density of superficial retinal plexus in the fovea (p = 0.0022) and parafovea (p < 0.0001) was significantly lower compared to Group one year and control group. In the deep retinal plexus, vascular density in the fovea (p = 0.0033) was significantly lower in both AMD groups compared to the control group, with no difference in the parafoveal region (p = 0.0774). The extent of non-flow area (p = 0.0003) and FAZ (p = 0.0008) were significantly larger in both AMD groups compared to the control group. There was a significant difference in CRT between those treated for one year and control eyes (p = 0.0036). CONCLUSIONS: In our study, we demonstrated that macular vessel density was lower in the foveal area in the superficial retinal plexus in AMD patients after one year and long-term anti-VEGF treatment. These vascular density changes were absent in the parafoveal and whole areas of the deep retinal plexus. Our results indicate that long-term anti-VEGF treatment reduces the vascular density of the superficial retinal plexus to a greater extent compared to the deep retinal plexus.

Novel Meibomian Gland and Tarsal Conjunctival Changes Associated with Trastuzumab, Pertuzumab, and Anastrozole Treatment for Metastatic HER2 Positive Breast Cancer: A Case Report and Literature Review.

The aim of the study was to report a case of severe meibomian gland dysfunction (MGD) and conjunctival changes associated with trastuzumab, pertuzumab, and anastrozole therapy in a HER-2 positive breast cancer patient. A 57-year-old white woman was treated with trastuzumab and pertuzumab biological and anastrozole endocrine therapy for metastatic breast cancer for several months. She suffered from intense eye pain and foreign body sensation. On the ocular surface, severe MGD developed without corneal lesions. On the tarsal conjunctiva, circumscribed lesions evolved 6 months after receiving anticancer therapy. After biopsy, the histological assessment excluded metastasis or chalazion. The lesion consisted of subepithelial lymphocytic infiltrates surrounding lipid-laden CD68-positive macrophages. Besides the redundant lipid accumulation, no acute necrotic reaction was seen. Noncontact infrared meibography visualized ductal drop-out in the upper and lower lids, and functional tests confirmed severe MGD. During the 18-month follow-up, the patient received treatment for MGD and no new conjunctival lesions developed, subjective symptoms subsided, and ocular surface morphology remained unchanged. The novel HER2-inhibitor trastuzumab and pertuzumab biological therapy and anastrozole endocrine therapy were associated with the disruption of the ocular surface milieu. The new histological aspect of tarsal conjunctiva changes may give a hint to understand the potential underlying molecular mechanisms of anticancer therapy-associated severe MGD. Since anticancer therapies may substantially interfere with the ocular surface milieu, awareness of this side effect leads to improved care of oncology patients.

Association between retinal vessel density and postoperative time after primary repair of rhegmatogenous retinal detachment.

The study aimed at a quantitative evaluation of macular vasculature after primary repair of rhegmatogenous retinal detachment (RRD) in correlation with the elapsed postoperative time. Optical coherence tomography angiography (OCT-A) was performed in 66 eyes of 33 patients in a retrospective case-control study: superficial and deep retinal vessel density (VD) of the whole image, fovea, parafovea, non-flow area, and foveal avascular zone (FAZ) were measured. Data of eyes with RRD were compared to the healthy fellow eyes in 3 groups according to the elapsed time after surgery: RD1: 6-12 months (n = 10), RD2: 1-2 years (n = 10), and RD3: 2-10 years (n = 13). In RD1 VD was significantly lower in the superficial parafoveal, deep parafoveal, and deep whole area compared to the fellow eyes. In RD3 VD was significantly lower in the superficial fovea, parafovea, whole image, and deep fovea, the non-flow area was significantly enlarged. OCT-A demonstrated a significant reduction in the superficial and deep regions of the macular vasculature after the repair of RRD. The deep area is more affected in the early postoperative period and the superficial region and the extent of the non-flow area are more involved after a longer postoperative time.

The Predictive Role of Thyroid Hormone Levels for Early Diabetic Retinal Changes in Experimental Rat and Human Diabetes.

Purpose: In diabetic subjects, early visual functional alterations such as color vision deficiencies (CVDs) are known to precede clinically apparent diabetic retinopathy. Prominent photoreceptor outer segment degeneration and an increase in the number of retinal dual cones (co-expressing S- and M-opsins simultaneously) have been described in diabetic rat models, suggesting a connection with the development of CVDs. As cone opsin expression is controlled by thyroid hormones, we investigated the diabetic retina in association with thyroid hormone alterations. Methods: In rat models of type 1 and 2 diabetes, dual cones were labeled by immunohistochemistry, and their numbers were analyzed in relation to free triiodothyronine (fT3) and free thyroxine (fT4) levels. Quantification of dual cones was also performed in human postmortem retinas. Additionally, a cross-sectional case-control study was performed where thyroid hormone levels were measured and color vision was assessed with Lanthony desaturated D15 discs. Results: A higher number of dual cones was detectable in diabetic rats, correlating with fT4 levels. Dual cones were also present in postmortem human retinas, with higher numbers in the three diabetic retinas. As expected, age was strongly associated with CVDs in human patients, and the presence of diabetes also increased the risk. However, the current study failed to detect any effect of thyroid hormones on the development of CVDs. Conclusions: Our results point toward the involvement of thyroid homeostasis in the opsin expression changes in diabetic rats and human samples. The evaluation of the possible clinical consequences warrants further research.

Rapid assessment of avoidable blindness-based healthcare costs of diabetic retinopathy in Hungary and its projection for the year 2045.

BACKGROUND/AIMS: The purpose of this study was to estimate the total healthcare cost associated with diabetic retinopathy (DR) in the population aged 18 years and older in Hungary, and its projection for the year 2045. METHODS: A cost model was developed based on the standardised rapid assessment of avoidable blindness with the diabetic retinopathy module (RAAB+DRM) methodology and recently reported prevalent-based cost of illness model. Projection for 2045 was made based on the estimation for increasing diabetes mellitus (DM) prevalence of the International Diabetes Federation. Costs were analysed from the perspective of the healthcare system and the patients. Our DR cost model was constructed according to the Scottish DR grading scale and based on the DR severity stadium. RESULTS: The total DR-associated healthcare cost was US$145.8 million in 2016 and will increase to US$169.0 million by 2045. The two major cost drivers were intravitreal antivascular endothelial growth factor injections and vitrectomies in this study (US$126.4 million in 2016 and US$146.5 million in 2045); they amounted to 86.7% of the total treatment cost of DR. The DR-related cost per patient was US$180.5 in Hungary. CONCLUSIONS: The cost per patient for treating DR was lower in Hungary than in other countries. Due to the increasing socioeconomic burden of proliferative DR and diabetes-related blindness, it would be important to invest in DR screening, prevention and early treatment. Our new RAAB-based cost of DR model may facilitate comparisons of DR treatment costs across countries.

Cataract blindness in Hungary.

AIM: To estimate the prevalence of blindness and visual impairment resulting from cataract in the population aged ≥50y in Hungary, and to assess the cataract surgical services. METHODS: A rapid assessment of avoidable blindness (RAAB) was conducted. A total of 3523 eligible people were randomly selected and examined. Each participant underwent surgery for cataract was interviewed with regard to the year, place, and costs of the surgery. Participants with obvious cataract were asked why they had not yet undergone surgery (barriers to surgery). RESULTS: An estimated 12 514 people were bilaterally blind; the visual acuity (VA) in 19 293 people was <6/60, and the VA in 73 962 people was <6/18 in the better eye due to cataract. An estimated 77 933 eyes are blind; 98 067 eyes had a VA of <6/60, and an estimated 277 493 eyes had a VA of <6/18 due to cataract. Almost all cataract surgeries were conducted in government hospitals. The age- and sex-adjusted cataract surgical coverage with VA<3/60 in eyes was 90.0%. The rate of good visual outcome after surgery was 79.5%. Ocular comorbidity was the main cause of poor outcome (78.1%), followed by late complications (such as posterior capsule opacification) (17.2%), inadequate optical correction (3.1%), and surgical complications (1.6%). The main barrier to surgery in people with bilateral cataract and VA of <6/60 was 'need not felt'. CONCLUSION: The prevalence of visual impairment resulting from cataract is slightly higher than expected. The quality of the cataract surgical service seems adequate in Hungary. However, the number of cataract operations per year should continue to increase due to the increasing patient demands and the aging population.

Evaluation of mechanical resistance to tearing of the anterior lens capsule after staining with different concentrations of trypan blue.

PURPOSE: To evaluate and compare the mechanical resistance to tearing of the anterior lens capsule opening after staining with different concentrations of trypan blue in ex vivo porcine eyes. SETTING: Semmelweis University, and Budapest University of Technology and Economics, Budapest, Hungary. DESIGN: Experimental study. METHODS: The study comprised 75 porcine eyes. The capsule was unstained in the Control Group (n = 25 eyes), 0.06% trypan blue was used to stain the capsule in Stained 1 Group (n = 25 eyes), and 0.1% trypan blue was used to stain the capsule in Stained 2 Group (n = 25 eyes). After capsulorhexis, the capsule openings were stretched with custom-designed testing equipment until they ruptured. The rupture force (RF), circumference stretching ratio (CSR), and secant modulus at 10 mN (SM10mN) and 50 mN (SM50mN) were evaluated. RESULTS: In total, 75 eyes were enrolled. There were no statistically significant differences in the RF (P = .8924) or CSR (P = .3876) among the groups. There were no statistically significant differences in the SM10mN (P = .8215) or SM50mN (P = .4184) among the groups. CONCLUSIONS: In this porcine eye model, the trypan blue concentrations that are routinely used in cataract surgery had no effect on capsular rim stability.

Vascular density in age-related macular degeneration after one year of antiVEGF treatment with treat-and-extend and fixed regimens.

Treatment of neovascular age-related macular degeneration (nAMD) with VEGF can be performed with several posologies. The purpose of our cross-sectional study was to analyze retinal vessel density by quantitative OCT-angiography (OCT-A) and to compare treat-and-extend (T&E) and fixed treatment protocols to a control group with dry AMD. Altogether 48 patients were enrolled: 13 eyes with T&E protocol ranibizumab treatment (group A) and 17 eyes with fixed regimen aflibercept therapy (group B), the control group comprised 18 eyes with dry AMD (group C). One year after the start of the treatment, quantitative OCT-A (AngioVue-Optovue, Fermont, USA) was performed: superficial and deep retinal vessel densities were analyzed in the foveal and parafoveal regions. Our results show, that the density of retinal superficial vasculature in the fovea was not different between the treatment groups (A: 25.9±9.1%; B: 24.3%±8.9), neither from group C (25.6±4.8%). Superficial parafoveal vascular density of the retina, however, was decreased in both treated groups (A: 46.7±9.1%, B: 42.9±6.1%, C: 49.7±4.9%). In the deep retinal plexus, vascular density was lower in both treatment groups compared to that of in controls in both the foveal and parafoveal area (A: 29.8±6.3%, B: 32.5±6.9%, C: 36.4±1.7% and A: 46.3±3.8%, B: 47.1±5.3%, C: 49.7±4.9%, foveal and parafoveal respectively). Our data suggest, that after one year of anti-VEGF treatment, reduced macular vessel density in three of the four examined vascular regions can be found independent of the treatment regimen.

Targeting neuronal and glial cell types with synthetic promoter AAVs in mice, non-human primates and humans.

Targeting genes to specific neuronal or glial cell types is valuable for both understanding and repairing brain circuits. Adeno-associated viruses (AAVs) are frequently used for gene delivery, but targeting expression to specific cell types is an unsolved problem. We created a library of 230 AAVs, each with a different synthetic promoter designed using four independent strategies. We show that a number of these AAVs specifically target expression to neuronal and glial cell types in the mouse and non-human primate retina in vivo and in the human retina in vitro. We demonstrate applications for recording and stimulation, as well as the intersectional and combinatorial labeling of cell types. These resources and approaches allow economic, fast and efficient cell-type targeting in a variety of species, both for fundamental science and for gene therapy.

Implantation of Scharioth macula lens in patients with age-related macular degeneration: results of a prospective European multicentre clinical trial.

OBJECTIVE: To report the visual and refractive outcomes following monocular implantation of a supplementary (piggyback) Scharioth macula lens (SML) in previously pseudophakic eyes with age-related macular degeneration (AMD). METHODS AND ANALYSIS: Prospective European multicentre clinical trial. 50 eyes of 50 pseudophakic patients with either dry or previously treated and stable neovascular AMD for at least 6 months were included. The inclusion criteria were age over 55, corrected distance visual acuity (CDVA) of 0.4-0.1 (decimal), improvement of at least three lines of corrected near visual acuity (CNVA) when tested with a +6.0 dioptre (D) reading addition at 15 cm, compared with a +2.5 D reading addition at 40 cm using a standardised, self-illuminated Early Treatment Diabetic Retinopathy Study near vision chart. The SML intraocular lens (IOL) was implanted as an add-on/piggyback IOL in the ciliary sulcus, monocularly in the better seeing eye of each subject meeting the inclusion criteria. RESULTS: There were no intraoperative complications. One subject had the SML explanted in the postoperative period due to postoperative glare/halos. The mean CNVA improved from 0.23±0.12 (decimal) preoperatively to 0.57±0.33 at 1 year. The mean CDVA remained unchanged measuring 0.19±0.13 preoperatively and 0.19±0.09 at 1 year postoperatively. CONCLUSION: The SML appears to be safe and effective in improving the CNVA in patients with AMD. Data suggest that the CDVA remains unaffected following implantation. Further data are needed to assess the long-term safety and efficacy.

Comparison of visual and refractive outcomes between hydrophilic and hydrophobic trifocal intraocular lenses sharing the same optical design.

PURPOSE: To compare clinical outcomes between two trifocal intraocular lenses (IOLs): the new FineVision POD F GF trifocal IOL made of hydrophobic acrylic glistening-free material, and the FineVision POD F IOL made of hydrophilic acrylic material with 26% water uptake in patients undergoing routine cataract surgery using standard phacoemulsification. SETTING: Semmelweis University, Department of Ophthalmology, Budapest, Hungary. DESIGN: Prospective controlled randomized single-center single-surgeon study. METHODS: Each patient had the hydrophilic POD F IOL implanted in one eye and the hydrophobic POD F GF IOL in the contralateral eye, according to a randomization table. Clinical outcomes included distance (4 m), intermediate (70 cm), and near (35 cm) visual acuities, contrast sensitivity measured under photopic and mesopic conditions, and defocus curves under photopic conditions. The follow-up was 6 months. RESULTS: The study comprised 25 patients. Under photopic conditions, there was no statistically significant difference between POD F GF and POD F IOLs for uncorrected distance (UDVA) (P = .607), uncorrected intermediate (UIVA) (P = .491), and uncorrected near (UNVA) (P = .414) visual acuities. Under mesopic conditions, there was no statistically significant differences between the 2 IOLs for UDVA (P = 1.00), UIVA (P = .149), and UNVA (P = .551). No statistically significant differences in contrast sensitivity were found between the groups under photopic (P = .4347) and mesopic (P = .425) conditions. No safety issues were reported. CONCLUSION: The study demonstrated equally good visual and refractive outcomes for the POD F GF IOL and the POD F IOL, giving the surgeon the option to choose the preferred material for the individual patient without compromising clinical outcomes.

Diabetes and blindness in people with diabetes in Hungary.

INTRODUCTION:: The purpose of the study was to estimate the number of people with diabetes mellitus, the prevalence of diabetes mellitus and the prevalence of blindness and severe visual impairment among people with diabetes mellitus in Hungary based on our recent national representative survey. METHODS:: Altogether 105 clusters of 35 people aged 50 years or older were randomly selected. Standardized rapid assessment of avoidable blindness with the diabetic retinopathy module was used. Each individual received a visual acuity assessment, and every person with diabetes mellitus underwent dilated fundus examination. RESULTS:: The estimated number of people with diabetes mellitus was 807,885 in the adult (⩾18 years) population in Hungary with 9.9% prevalence. Diabetic retinopathy exhibited an increasing tendency with age. The prevalence rates of blindness and severe visual impairment in people with diabetes mellitus aged ⩾50 years were 1.0% and 0.9%, respectively. Diabetic retinopathy was responsible for 28% of blindness and 50% of severe visual impairment among participants aged ⩾50 years with diabetes mellitus. CONCLUSION:: The estimated number of people with diabetes mellitus and prevalence of diabetes mellitus were lower than those recently reported. However, if we extend our estimation, prevalence of undiagnosed diabetes mellitus may be higher and thus prevalence of diabetes mellitus may reach a higher value (between 9.9% and 13.4%). Because of the high number of ophthalmologically uncontrolled diabetic eyes and high rate of blindness due to diabetic retinopathy, primary eye care should be improved, and a nationwide telemedical eye-screening programme should be undertaken.

Randomized controlled European multicenter trial on the prevention of cystoid macular edema after cataract surgery in diabetics: ESCRS PREMED Study Report 2.

PURPOSE: To compare the efficacy of perioperative treatment strategies, in addition to topical bromfenac 0.09% and dexamethasone 0.1%, to reduce the risk for developing cystoid macular edema (CME) after uneventful cataract surgery in diabetic patients. SETTING: Twelve European study centers. DESIGN: Randomized clinical trial. METHODS: Diabetic patients having phacoemulsification cataract surgery were randomly allocated to receive no additional treatment, a subconjunctival injection with 40 mg triamcinolone acetonide, an intravitreal injection with 1.25 mg bevacizumab, or a combination of both. The main outcomes were the difference in central subfield mean macular thickness, corrected distance visual acuity, and the incidence of CME and clinically significant macular edema within 6 and 12 weeks postoperatively. RESULTS: The study comprised 213 patients. At 6 and 12 weeks postoperatively, the central subfield mean macular thickness was 12.3 µm and 9.7 µm lower, respectively, in patients who received subconjunctival triamcinolone acetonide than patients who did not (P = .007 and P = .014, respectively). No patient who received subconjunctival triamcinolone acetonide developed CME. Intravitreal bevacizumab had no significant effect on macular thickness. CONCLUSIONS: Diabetic patients who received a subconjunctival injection with triamcinolone acetonide at the end of cataract surgery had a lower macular thickness and macular volume at 6 and 12 weeks postoperatively than patients who did not. Intravitreal bevacizumab had no significant effect.

The Effect of Tear Supplementation with 0.15% Preservative-Free Zinc-Hyaluronate on Ocular Surface Sensations in Patients with Dry Eye.

PURPOSE: To evaluate the effect of tear supplementation with preservative free 0.15% zinc-hyaluronate on ocular surface sensations and corneal sensitivity in dry eye patients. METHODS: Ocular surface sensations were assessed using the ocular surface disease index (OSDI) questionnaire and by recording ocular sensations during forced blinking in parallel with noninvasive tear film breakup time measurement in 20 eyes of 20 dry eye patients. Corneal sensitivity thresholds to selective stimulation of corneal mechano-, thermal- and chemical receptors were measured using the Belmonte gas esthesiometer. All baseline measurements were repeated after 1 month of treatment with 0.15% zinc-hyaluronate. RESULTS: After 1 month, a significant decrease in mean OSDI score (from 35.66 ± 12.36 to 15.03 ± 11.22; P < 0.001) and a significant improvement in tear film breakup time (from 3.83 ± 0.80 to 8.67 ± 4.50 s; P < 0.001) was observed compared to baseline. Sensory responses during the interblink period also significantly decreased after 1 month (P < 0.004). Corneal sensitivity thresholds to mechanical stimulation (90.61 ± 20.35 vs. 103.92 ± 17.97 mL/min; P < 0.025) and chemical stimulation (33.21 ± 0.51 vs. 33.58% ± 0.44% CO2; P < 0.025) significantly increased after 1 month, however sensitivity thresholds to thermal stimulation remained unchanged compared to baseline (P > 0.05). CONCLUSION: Prolonged use of 0.15% zinc-hyaluronate results in an improvement of tear film stability and a decrease of dry eye complaints. The decrease in corneal mechano-and polymodal receptor excitability suggests that zinc-hyaluronate helps to recover normal corneal sensitivity, and thus might have a beneficial additional effect on reducing ocular surface complaints in dry eye patients.