Prevalence and Associations of Nonglaucomatous Optic Nerve Atrophy in High Myopia: The Ural Eye and Medical Study.

PURPOSE: To assess the prevalence of nonglaucomatous optic nerve atrophy (NGOA) in highly myopic individuals. DESIGN: Population-based study. PARTICIPANTS: The Ural Eye and Medical Study included 5899 (80.5%) of 7328 eligible individuals (80.5%). METHODS: Nonglaucomatous optic nerve atrophy, graded into 5 arbitrary stages, was characterized by decreased visibility of the retinal nerve fiber layer (RNFL) on photographs, neuroretinal rim pallor, abnormally thin retinal arteriole diameter, and abnormally thin peripapillary RNFL as measured by OCT. MAIN OUTCOME MEASURES: Nonglaucomatous optic nerve atrophy prevalence and degree. RESULTS: Of 5709 participants (96.9%) with axial length measurements, 130 individuals (2.3%) were highly myopic, of whom 116 individuals (89.2%; age, 57.8 ± 11.1 years; axial length, 27.0 ± 1.2 mm) had available fundus photographs and OCT images and were included into the study. Nonglaucomatous optic nerve atrophy prevalence was 34/116 individuals (29.3%; 95% confidence interval [CI], 21.0-38.0), and mean NGOA degree in eyes with NGOA was 1.7 ± 1.0 arbitrary units. Higher NGOA degree correlated (multivariable analysis; regression coefficient, r2 = 0.59) with longer axial length (ß, 0.22; P = 0.007), wider temporal parapapillary γ zone width (ß, 0.50; P < 0.001), higher prevalence of diabetes (ß, 0.20; P = 0.005), and higher systolic blood pressure (ß, 0.15; P = 0.03). Higher NGOA prevalence was associated with longer axial length (odds ratio [OR], 7.45; 95% CI, 2.15-25.7), wider temporal parapapillary γ zone (OR, 6.98; 95% CI, 2.61-18.7), and higher systolic blood pressure (OR, 1.05; 95% CI, 1.01-1.10). CONCLUSIONS: In this ethnically mixed population from Russia with an age of 40 years or more, high axial myopia showed a relatively high prevalence of NGOA, increasing with longer axial length and wider temporal parapapillary γ zone. For each 1 mm of axial elongation and γ zone widening, the odds for NGOA increased 7.45-fold and 6.98-fold, respectively. The axial elongation-associated and γ zone-related increase in the distance between the retinal ganglion cells and the optic disc may lead to a lengthening and stretching of the retinal ganglion cell axons and may be of importance pathogenetically. In highly myopic eyes, NGOA may be a reason for visual field and central visual acuity loss, unexplainable by myopic macular pathologic features. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Diabetic Neuropathy of the Retina and Inflammation: Perspectives.

A clear connection exists between diabetes and atherosclerotic cardiovascular disease. Consequently, therapeutic approaches that target both diseases are needed. Clinical trials are currently underway to explore the roles of obesity, adipose tissue, gut microbiota, and pancreatic beta cell function in diabetes. Inflammation plays a key role in diabetes pathophysiology and associated metabolic disorders; thus, interest has increased in targeting inflammation to prevent and control diabetes. Diabetic retinopathy is known as a neurodegenerative and vascular disease that occurs after some years of poorly controlled diabetes. However, increasing evidence points to inflammation as a key figure in diabetes-associated retinal complications. Interconnected molecular pathways, such as oxidative stress, and the formation of advanced glycation end-products, are known to contribute to the inflammatory response. This review describes the possible mechanisms of the metabolic changes in diabetes that involve inflammatory pathways.

Prevalence and Associated Factors of Diabetic Retinopathy in a Russian Population. The Ural Eye and Medical Study.

AIM: To assess prevalence and associated factors of diabetic retinopathy (DR) in a Russian population. METHODS: Out of 7328 eligible individuals, the population-based cross-sectional Ural Eye and Medical Study included 5899 (80.5%) individuals aged 40+ years, who underwent a detailed medical and ophthalmological examination. Using ocular fundus photographs and optical coherence tomographic images, we assessed prevalence and degree of DR in 5105 participants. RESULTS: DR was present in 99/5105 individuals (1.9%; 95% confidence interval [CI]: 1.6, 2.3). Its prevalence increased from 6/657 (1.0%; 95% CI: 0.2, 1.6) in the age group of 45-50 years to 24/680 (3.5%; 95% CI: 2.1, 4.9) in the age group of 65-70 years, and decreased to 3/153 (2.0%; 95% CI: 0.00, 4.2) in the age group of 80+ years. DR prevalence within the 577 (11.4%; 95% CI: 10.5, 12.2) individuals with diabetes was 99/577 (17.2%; 95% CI: 14.1, 20.2). DR was the cause for moderate-to-severe vision impairment (best corrected visual acuity <6/18 but ≥3/60) in four individuals (4/5105; 0.07%). In multivariable analysis, higher DR prevalence was associated with higher serum glucose concentration (odds ratio [OR]: 1.30; 95% CI: 1.20, 141), longer diabetes duration (OR: 1.06; 95% CI: 1.02, 1.09), type of diabetes therapy (nil/diet/oral/insulin) (OR:4.19;95% CI:3.08, 5.70), lower educational level (OR:0.81;95% CI:0.67, 0.98), lower manual dynamometric force (OR: 0.96; 95% CI: 0.94, 0.99), shorter ocular axial length (OR: 0.73; 95% CI: 0.56, 0.96), and higher diastolic blood pressure (OR: 1.04; 95% CI: 1.01, 1.06), or alternatively, higher estimated cerebrospinal fluid pressure (OR: 1.09; 95% CI: 1.01, 1.18). CONCLUSION: In this urban and rural Russian population aged 40+ years, DR prevalence was relatively low (1.9%; 95% CI: 1.6, 2.3), showed an inverted U-shaped association with age, and in a cross-sectional study design it was associated with shorter axial length and higher estimated cerebrospinal fluid pressure.

Prevalence of Myopic Maculopathy Among Adults in a Russian Population.

Importance: Although myopic maculopathy has become a major cause of vision impairment worldwide, few data from Russia and Central Asia on the prevalence of myopic maculopathy have been available. Objective: To assess the prevalence of myopic maculopathy and its associations with ocular and systemic parameters in a population in Russia. Design, Setting, and Participants: The Ural Eye and Medical Study, a population-based case-control study, was conducted in rural and urban areas in Bashkortostan, Russia, from October 26, 2015, to July 4, 2017. Data analysis was performed from September 13 to September 15, 2019. The Ural Eye and Medical Study included 5899 of 7328 eligible individuals (80.5%) aged 40 years or older. Exposures: A detailed ocular and systemic examination included fundus photography and optic coherence tomography for the assessment of myopic maculopathy. Main Outcomes and Measures: Prevalence of myopic maculopathy. Results: The present investigation included 5794 of the 5899 eligible individuals (98.2%; 3277 [56.6%] women; mean [SD] age, 58.9 [10.7] years) with available information about myopic maculopathy. Mean (SD) axial length was 23.3 (1.1) mm (range, 19.78-32.87 mm). Prevalence of any myopic maculopathy was 1.3% (95% CI, 1.0%-1.6%); myopic maculopathy stage 2, 0.8% (95% CI, 0.6%-10.0%); stage 3, 0.2% (95% CI, 0.1%-0.4%); and stage 4, 0.2% (95% CI, 0.1%-0.4%). The prevalence of moderate to severe vision impairment and blindness was 29.8% (14 of 47 participants; 95% CI, 16.2%-43.3%) in stage 2 myopic maculopathy, 57.1% (8 of 14 participants; 95% CI, 27.5%-86.8%) in stage 3, and 100% (13 of 13 participants; 95% CI, 100%-100%) in stage 4. In multivariable analysis, a higher myopic maculopathy prevalence was associated with longer axial length (odds ratio [OR], 4.54; 95% CI, 3.48-5.92; P < .001), older age (OR, 1.04; 95% CI, 1.01-1.07; P = .03), and thinner peripapillary retinal nerve fiber layer thickness (OR, 0.96; 95% CI, 0.95-0.98; P < .001). After exclusion of glaucomatous eyes, the association between myopic maculopathy prevalence and thinner retinal nerve fiber layer remained significant (OR, 0.96; 95% CI, 0.95-0.98; P < .001). Myopic maculopathy prevalence was not significantly associated with sex; region of habitation; level of education; ethnicity; prevalence of arterial hypertension, chronic obstructive pulmonary disease, chronic kidney disease, diabetes, and inflammatory liver disease; hearing loss; depression score; or anxiety score. Conclusions and Relevance: In this ethnically mixed population from Russia, myopic maculopathy prevalence was mainly associated with elongated axial length and thinner peripapillary retinal nerve fiber layer, but was not associated with any major internal medical disease, level of education, ethnicity, or sex. Higher myopic maculopathy stage was associated with vision impairment and blindness. In addition to a known association between high axial myopia and glaucoma, myopic maculopathy may be associated with nonglaucomatous optic neuropathy.

Prevalence and Associated Factors of Age-Related Macular Degeneration in a Russian Population: The Ural Eye and Medical Study.

PURPOSE: To assess the prevalence of age-related macular degeneration (AMD) in a Russian population. DESIGN: Population-based prevalence assessment. METHODS: The Ural Eye and Medical Study was conducted in a rural and urban area in the Russian republic of Bashkortostan. The study included 5,899 participants aged 40+ years old. AMD, defined according to the Beckman Initiative for Macular Research, was assessed by fundus photographs and optical coherence tomographic images of 4,932 (83.6%) participants. RESULTS: The prevalence of any AMD, early AMD, intermediate AMD, or late AMD, geographic atrophy, and neovascular AMD were 18.2% (95% confidence interval [CI], 16.8-19.6), 11.6% (95% CI, 10.4-12.8), 5.0% (95% CI, 4.2-5.8), 1.6% (95% CI, 1.1-2.0), 0.7% (95% CI, 0.4-1.0) and 0.9% (95% CI, 0.6-1.3), respectively, for individuals >55 years old. Applying an age limit of 40+ years for the AMD definition, prevalence of any AMD, early AMD, intermediate AMD, late AMD, geographic atrophy and neovascular AMD were 14.1% (95% CI, 13.1-15.1), 9.4% (95% CI, 8.6-10.2), 3.8% (95% CI, 3.2-4.3), 1.0% (95% CI, 0.7-1.2), 0.4% (95% CI, 0.2-0.6) and 0.5% (95% CI, 0.3-0.7), respectively, for individuals aged 40+ years. Higher AMD prevalence was correlated with older age (odds ratio [OR], 1.15; 95% CI, 1.13-1.16; P < 0.001), rural region (OR, 1.69; 95% CI, 1.32-2.17; P < 0.001), lower diabetes prevalence (OR, 0.56; 95% CI, 0.38-0.82; P = 0.003), and shorter axial length (OR, 0.89; 95% CI, 0.79-0.99; P = 0.04). AMD prevalence was not significantly (all P ≥ 0.20) correlated with any systemic parameter examined, except for lower prevalence of diabetes. CONCLUSIONS: In this typical, ethnically mixed, urban and rural population from Russia, a higher prevalence for AMD was associated mainly with older age, rural region of habitation, shorter axial length, and lower prevalence of diabetes mellitus. The AMD prevalence was lower than in Europeans and higher than in East Asians.

Prevalence and Associated Factors of Pseudoexfoliation in a Russian Population: The Ural Eye and Medical Study.

PURPOSE: To assess the prevalence of pseudoexfoliation (PEX) and its associations in a Russian population. DESIGN: Population-based cross-sectional study. METHODS: Setting: Ufa capital of Bashkortostan, Russia and a rural region in Bashkortostan. PARTICIPANTS: the Ural Eye and Medical Study included 5,899 (80.5%) of 7,328 eligible individuals (mean age, 59.0 ± 10.7 years old; range, 40-94 years). OBSERVATION PROCEDURES: as part of an ophthalmological and general examination, presence and degree of PEX was assessed using slit-lamp biomicroscopy after medical pupillary dilation. MAIN OUTCOME MEASUREMENTS: PEX prevalence. RESULTS: After excluding pseudophakic and aphakic individuals, the study included 5,451 (92.4%) participants. PEX prevalence (3.6%; 95% confidence interval [CI]:3.1-4.1), increased from 0.5% (95% CI, 0.1-0.9) in individuals 40 to <50 years old to 10.4% (95% CI, 5.0-15.8) in individuals aged 80+ years. Higher PEX prevalence was associated (multivariate analysis) with older age (odds ratio [OR], 1.09; 95% CI, 1.07-1.11; P < 0.001), Russian ethnicity (OR, 1.50; 95% CI, 2.09-1.11;P = 0.02), higher prevalence of open-angle glaucoma (OR, 2.40; 95% CI, 1.36-4.23;P = 0.003), and higher intraocular pressure (OR, 1.06; 95% CI, 1.02-1.09;P = 0.001). PEX prevalence was not significantly associated with gender (P = 0.49), region of habitation (P = 0.11), body mass index (P = 0.68), level of education (P = 0.26), smoking (P = 0.11), alcohol consumption (P = 0.52), history of cardiovascular or cerebrovascular disease (P = 0.94) and dementia (P = 0.77), prevalence of diabetes mellitus (P = 0.16), arterial hypertension (P = 0.45), chronic obstructive pulmonary disease (P = 0.73), chronic kidney disease (P = 0.09), and hearing loss (P = 0.31). CONCLUSIONS: In this typical, ethnically mixed, population from Russia with an age of 40+ years, PEX prevalence (3.6%; 95% CI, 3.1-4.1) was associated with older age, Russian ethnicity, higher intraocular pressure and open-angle glaucoma. It was independent of any systemic parameter including diabetes, arterial hypertension, previous cardiovascular and cerebrovascular diseases and dementia.

Pathogenesis and Management of Macular Hole: Review of Current Advances.

Macular hole has been believed to be a disorder of vitreomacular interface, which forms as a result of abnormal vitreous traction from incomplete vitreous detachment. However, our recent studies demonstrated that dynamic forces, caused by mobile posterior cortical vitreous with fluid currents, exist already at early stages of macular hole development. Therefore, in eyes with flexible vitreous, the contributions of tractional forces due to vitreous shrinkage are unlikely. These facts indicate that in the development of idiopathic macular holes, there is a greater contribution of dynamic forces than has been previously reported. This review also evaluates the recent findings in the assessment of the idiopathic macular holes and the recent therapeutic strategies for optimal management. Inner limiting membrane is considered to improve anatomical closure rate; however, it is still questionable if peeling is necessary in holes less than 250 µm. There are plenty of publications indicating that in the management of small and medium size hole (less than 400 µm), use of long-lasting gas and face-down position is not always required; however, it may be necessary for the treatment of large holes. Ocriplasmin and expansile gas had been reported to be successful for management of small- and medium-sized holes and vitreomacular attachment.

Axial length and its associations in a Russian population: The Ural Eye and Medical Study.

PURPOSE: To assess the normal distribution of axial length and its associations in a population of Russia. METHODS: The population-based Ural Eye and Medical Study included 5,899 (80.5%) individuals out of 7328 eligible individuals aged 40+ years. The participants underwent an ocular and systemic examination. Axial length was measured sonographically (Ultra-compact A/B/P ultrasound system, Quantel Medical, Cournon d'Auvergne, France). RESULTS: Biometric data were available for 5707 (96.7%) individuals with a mean age of 58.8±10.6 years (range:40-94 years; 25%, 50%, 75% quartile: 51.0, 58.0, 66.0 years, respectively). Mean axial length was 23.30±1.10 mm (range: 19.02-32.87mm; 95% confidence interval (CI): 21.36-25.89; 25%, 50%, 75% quartile: 22.65mm, 23.23mm, 23.88mm, resp.). Prevalences of moderate myopia (axial length:24.5-<26.5mm) and high myopia (axial length >26.5mm) were 555/5707 (8.7%;95%CI:9.0,10.5) and 78/5707 (1.4%;95%CI:1.1,1.7), respectively. Longer axial length (mean:23.30±1.10mm) was associated (correlation coefficient r2:0.70) with older age (P<0.001;standardized regression coefficient beta:0.14), taller body height (P<0.001;beta:0.07), higher level of education (P<0.001;beta:0.04), higher intraocular pressure (P<0.001;beta:0.03), more myopic spherical refractive error (P<0.001;beta:-0.55), lower corneal refractive power (P<0.001;beta:-0.44), deeper anterior chamber depth (P<0.001;beta:0.20), wider anterior chamber angle (P<0.001;beta:0.05), thinner peripapillary retinal nerve fiber layer thickness (P<0.001;beta:-0.04), higher degree of macular fundus tessellation (P<0.001;beta:0.08), lower prevalence of epiretinal membranes (P = 0.01;beta-0.02) and pseudoexfoliation (P = 0.007;beta:-0.02) and higher prevalence of myopic maculopathy (P<0.001;beta:0.08). In that model, prevalence of age-related macular degeneration (any type: P = 0.84; early type: P = 0.46), diabetic retinopathy (P = 0.16), and region of habitation (P = 0.27) were not significantly associated with axial length. CONCLUSIONS: Mean axial length in this typically multi-ethnic Russian study population was comparable with values from populations in Singapore and Beijing. In contrast to previous studies, axial length was not significantly related with the prevalences of age-related macular degeneration and diabetic retinopathy or region of habitation.

In vivo effects of single or combined topical neuroprotective and regenerative agents on degeneration of retinal ganglion cells in rat optic nerve crush model.

To determine the effectiveness of a single or a combination of topical neurotrophic factors (NFs) in protecting retinal ganglion cells (RGCs) in the rat optic nerve crush (ONC) model, the left ONC was performed to induce the death of the RGCs in adult Sprague-Dawley rats. The NFs studied were tauroursodeoxycholic acid (TUDCA), citicoline, neurotrophin-4 (NT-4), combined TUDCA/citicoline (Doublet-1), combined TUDCA/NT-4 (Doublet-2), combined TUDCA/citicoline/NT-4 (Triplet), and PBS. After 2 weeks, the number of RGCs was determined by Brn3a immunostaining. The optic nerves were immunostained for anti-Growth Associated Protein-43(GAP-43) and -200kD neurofilament heavy antibody to study optic nerve regeneration. Two weeks after the ONC, the densities of RGCs in all treated eyes were significantly higher than that of the PBS treated eyes. In the Triplet group, the number of RGC axons after ONC was significantly higher than that in all of the single treatment groups and the number of TUNEL positive cells was significantly reduced and the number of GAP-43 immunopositive axons was significantly greater than those in the PBS group. Neovascularization was observed only in the Doublet-1 group. We conclude that the combination of the three NFs was the most effective way to protect RGCs after the ONC.

Diabetic corneal neuropathy: clinical perspectives.

Diabetic keratopathy is characterized by impaired innervation of the cornea that leads to decreased sensitivity, with resultant difficulties with epithelial wound healing. These difficulties in wound healing put patients at risk for ocular complications such as surface irregularities, corneal infections, and stromal opacification. Pathological changes in corneal innervations in diabetic patients are an important early indicator of diabetic neuropathy. The decrease in corneal sensitivity is strongly correlated with the duration of diabetes as well as the severity of the neuropathy. This review presents recent findings in assessing the ocular surface as well as the recent therapeutic strategies for optimal management of individuals with diabetes who are susceptible to developing diabetic neuropathy.

Complete corneal ring (MyoRing) implantation versus MyoRing implantation combined with corneal collagen crosslinking for keratoconus: 3-year follow-up.

PURPOSE: To estimate the effectiveness of complete corneal ring (MyoRing) implantation compared with MyoRing implantation combined with corneal collagen crosslinking (CXL) for keratoconus treatment for 36 months follow-up. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: MyoRing implantation was performed in a series of 78 patients (80 eyes) with keratoconus II-III Amsler classification, of these 39 eyes had MyoRing implantation combined with CXL. Implantation of a MyoRing in the corneal pocket was performed using a PocketMaker microkeratome and corneal intrastromal implantation system. During CXL, riboflavin solution 0.1% was injected into the corneal pocket through the incision tunnel and standard surface UVA irradiation (370 nm, 3 mW/cm2) was then applied from 5-cm distance for 30 min. RESULTS: Significant improvements in uncorrected distance visual acuity and corrected distance visual acuity were observed for both groups, which was relatively better 12 months after procedure in MyoRing alone group; however, in 36 months there was no difference between groups. Keratometry was reduced in both groups; after MyoRing implantation for 8.45 D and MyoRing + CXL for 9.43 D, the spherical equivalent decreased from 8.45 to 7.72 D and from 9.43 to 6.25 D, respectively. The cylinder decreased to 3.33 D with MyoRing alone and to 3.31 D with MyoRing + CXL. Corneal thickness remained nearly unchanged (from 433.69 ± 38.76 to 434.21 ± 34.98) in MyoRing group and decreased from baseline (from 426.93 ± 46.58 to 401.24 ± 39.12 µm) in MyoRing + CXL group 36 months postoperatively, which corresponds with pachymetry reduction after conventional CXL. CONCLUSION: Both MyoRing implantation and MyoRing combined with CXL were effective for treating keratoconus. At 36 months, there were slightly better outcomes in MyoRing + CXL group; however, in MyoRing alone group visual and refractive outcomes were stable overtime.

Combination of Neuroprotective and Regenerative Agents for AGE-Induced Retinal Degeneration: In Vitro Study.

To determine the most effective combination of neuroprotective and regenerative agents for cultured retinal neurons from advanced glycation end products- (AGEs-) induced degeneration, retinal explants of 7 adult Sprague-Dawley rats were three-dimensionally cultured in collagen gel and incubated in serum-free media and in 7 media; namely, AGEs, AGEs + 100 µM citicoline, AGEs + 10 ng/mL NT-4, AGEs + 100 µM TUDCA, AGEs + 100 µM citicoline + TUDCA (doublet), and AGEs + 100 µM citicoline + TUDCA + 10 ng/mL NT-4 (triplet) were examined. The number of regenerating neurites was counted after 7 days of culture, followed by performing TUNEL and DAPI staining. The ratio of TUNEL-positive cells to the number of DAPI-stained nuclei was calculated. Immunohistochemical examinations for the active form of caspase-9 and JNK were performed. All of the neuroprotectants increased the number of neurites and decreased the number of TUNEL-positive cells. However, the number of neurites was significantly higher, and the number of TUNEL-positive cells and caspase-9- and JNK-immunopositive cells was fewer in the retinas incubated with the combined three agents. Combination solutions containing citicoline, TUDCA, and NT-4 should be considered for neuroprotective and regenerative therapy for AGE-related retinal degeneration.

Mechanisms of Neuronal Cell Death in AGE-exposed Retinas - Research and Literature Review.

INTRODUCTION: Accelerated formation of AGE due to increasing rise in blood glucose levels leads to developments of metabolic changes, further leading to such complications as diabetic retinopathy which is a major reason of leading to blindness and affecting working population worldwide. BACKGROUND: The results of recent investigations have demonstrated that the death of retinal ganglion cells (RGCs) and their axons is the common pathological changes in AGE-exposed retina and the possible mechanisms that are responsible for the onset and progression of RGC death and axonal degeneration in patients with diseases associated with AGEs accumulation are represented in this review. Identifying the mechanisms of the onset and the progression of RGC neuropathy can help in discovering the pathogenetic orientated treatment. OBJECTIVE: This review describes recently discovered possible mechanisms of diabetic retinopathy obtained by laboratory studies with the suggestion that AGEs play an important role in the pathogenesis of diabetic retinal neuropathy triggering different mechanisms that result in neuronal dysfunction. For searching therapeutic approach the regenerative effect of different neurotrophic factors has been studied such as neurotrophin-4, hepatocyte growth factor, glial cell line-derived neurotrophic factor, and Tauroursodeoxycholic acid. CONCLUSION: The findings for the establishment of neuroprotective and regenerative therapies for AGE-related diseases including diabetic retinopathy are represented in this review.

Standard corneal collagen crosslinking versus transepithelial iontophoresis-assisted corneal crosslinking, 24 months follow-up: randomized control trial.

PURPOSE: To compare the results of standard corneal crosslinking (CXL) and transepithelial iontophoresis-assisted CXL after 24 months follow-up. MATERIAL AND METHODS: Corneal crosslinking (CXL) was performed in a series of 149 eyes of 119 patients with keratoconus I-II of Amsler classification. Depending on the CXL method, patients were divided into two groups: (1) 73 eyes with standard CXL and (2) 76 eyes with transepithelial iontophoresis-assisted CXL. Depending on the group, epithelium removal or administration of riboflavin solution by iontophoresis for 10 min was performed, after which standard surface UVA irradiation (370 nm, 3 mW/cm2 ) was performed at a 5-cm distance for 30 min. RESULTS: A statistically significant difference in corrected distance visual acuity (CDVA) was observed between the two groups, with a better outcome in the second group after 6 months (p = 0.037); however, no significant difference was found 24 months after treatment (p = 0.829). Stabilization and regression of keratometry values were achieved in both groups, but standard CXL was more effective. The average demarcation line depth in the standard CXL group was 292 ± 14 µm after 14 days and 172 ± 16 µm in the transepithelial iontophoresis-assisted CXL group. No demarcation line was detected after 1 month and 3 months in 45% and 100% of the eyes in the second group respectively. CONCLUSION: Transepithelial iontophoresis-assisted collagen crosslinking showed to be less effective than standard CXL after 24 months of follow-up, possibly due to a more superficial formation of corneal collagen crosslinks, however the stopping of disease progression was achieved 24 months after procedure.

Neuronal Changes in the Diabetic Cornea: Perspectives for Neuroprotection.

Diabetic neuropathy is associated with neurotrophic ulcerations of the skin and cornea. Decreased corneal sensitivity and impaired innervation lead to weakened epithelial wound healing predisposing patients to ocular complications such as corneal infections, stromal opacification, and surface irregularity. This review presents recent findings on impaired corneal innervation in diabetic individuals, and the findings suggest that corneal neuropathy might be an early indicator of diabetic neuropathy. Additionally, the recent findings for neuroprotective and regenerative therapy for diabetic keratopathy are presented.

Altered Expression of NF- κ B and SP1 after Exposure to Advanced Glycation End-Products and Effects of Neurotrophic Factors in AGEs Exposed Rat Retinas.

To determine the effect of advanced glycation end-products (AGEs) on neurite regeneration, and also to determine the regenerative effects of different neurotrophic factors (NTFs) on rat retinal explants, the retinas of SD rats were cultured in three-dimensional collagen gels and incubated in 6 types of media: (1) serum-free control culture media; (2) 100 µg/mL AGEs-BSA media; (3) AGEs-BSA + 100 ng/mL neurotrophin-4 (NT-4) media; (4) AGEs-BSA + 100 ng/mL hepatocyte growth factor media; (5) AGEs-BSA + 100 ng/mL glial cell line-derived neurotrophic factor media; or (6) AGEs-BSA + 100 µM tauroursodeoxycholic acid media. After 7 days, the number of regenerating neurites was counted. The explants were immunostained for nuclear factor-κB (NF-κB) and specificity protein 1 (SP1). Statistical analyses were performed by one-way ANOVA. In retinas incubated with AGEs, the numbers of neurites were fewer than in control. All of the NTFs increased the number of neurites, and the increase was more significant in the NT-4 group. The number of NF-κB and SP1 immunopositive cells was higher in retinas exposed to AGEs than in control. All of the NTFs decreased the number of NF-κB immunopositive cells but did not significantly affect SP1 expression. These results demonstrate the potential of the NTFs as axoprotectants in AGEs exposed retinal neurons.

Neurotrophic factors for retinal ganglion cell neuropathy - with a special reference to diabetic neuropathy in the retina.

Diabetes mellitus is a disease with a devastating impact on population. Recent data revealed that early retinal neuropathy in patients with diabetic retinopathy involved a reduced expression of brain-derived neurotrophic factor. Retinal ganglion cells (RGC) neuropathy is a progressive optic nerve neuropathy with RGC death and axonal degeneration, and it leads to blindness in the elderly population worldwide. Thus, neuroprotective therapies that rescue damaged RGCs and inhibit the progression of RGC loss and axonal degeneration are needed. This review introduces potential neuroprotective therapies using different neurotrophic factors for damaged RGC in eyes with RGC neuropathy associated diseases.

One-year results of intravitreal ranibizumab combined with reduced-fluence photodynamic therapy for polypoidal choroidal vasculopathy.

PURPOSE: To compare the 1-year results of intravitreal ranibizumab combined with reduced-fluence photodynamic therapy (RF-PDT) to intravitreal ranibizumab (IVR) alone for eyes with polypoidal choroidal vasculopathy (PCV). METHODS: We reviewed the medical records from 47 consecutive patients with PCV (47 naïve eyes). Seventeen eyes from 17 patients had one IVR treatment combined with RF-PDT followed by two additional IVR treatments (combined group), and 30 eyes from 30 patients were treated with 3 monthly IVR treatments (IVR group). All eyes had a follow-up period of at least 12 months. RESULTS: At 12 months, the mean logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) significantly improved from 0.55 to 0.38 logMAR units in the combined group (P=0.041) but did not change significantly in the IVR group (P=0.371). The central foveal thickness (CFT) was significantly thinner in both groups at 6 months (P<0.01). Additional IVR injections were required less frequently in the combined group (n=3; 17%) than in the IVR group (n=16; 53%) during the 12 month follow-up (P=0.029). CONCLUSION: The IVR and RF-PDT combination led to significant BCVA improvements and required fewer additional IVR treatments for at least 12 months in eyes with PCV.

Level of vascular endothelial growth factor 165b in human aqueous humor.

PURPOSE: Vascular endothelial growth factor 165b (VEGF165b) is a splice variant of VEGF-A and is an anti-angiogenic form as opposed to a pro-angiogenic form of VEGF. We compared the level of VEGF165b in the aqueous humor of 77 eyes with exudative age-related macular degeneration (AMD) and 38 eyes with retinal vein occlusion (RVO). DESIGN: A prospective, interventional case series. METHODS: The concentration of aqueous VEGF165b was measured by enzyme-linked immunosorbent assay (ELISA), and its level in the subgroups of AMD, classic and occult choroidal neovascularization (CNV) and polypoidal choroidal vasculopathy (PCV), was compared. The relationships between the VEGF165b level and the greatest linear dimension (GLD), central foveal thickness (CFT), and the height of the subretinal fluid (SRF) were determined for the AMD and RVO cases. RESULTS: The level of VEGF165b was higher than the lower limit of detection (15 pg/ml) in 57% of the AMD cases (median, 16.4; range, <15-98 pg/ml) and 63% of the controls (median, 20.6; range, <15-46 pg/ml). The percentage of eyes with >15 pg/ml of VEGF165b was significantly lower in eyes with RVO (32%, p = 0.038). The VEGF165b level was not significantly different among the AMD subtypes, and it was not significantly correlated with the GLD, CFT, and SRF. In the RVO cases, the CFT and SRF thickness were greater in eyes with a VEGF level <15 pg/ml (p = 0.006, 0.048 respectively). CONCLUSIONS: The anti-angiogenic VEGF165b was low in eyes with RVO. Therapy based on balancing the pro- and anti-angiogenic factors might be a new approach to treat ocular vascular disorders.