Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future.

PURPOSE: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. DESIGN: Meta-analysis of prevalence data. PARTICIPANTS: A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. METHODS: AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). MAIN OUTCOME MEASURES: Prevalence of early and late AMD, BCVA, and number of AMD cases. RESULTS: Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%-5.0%) in those aged 55-59 years to 17.6% (95% CI 13.6%-21.5%) in those aged ≥85 years; for late AMD these figures were 0.1% (95% CI 0.04%-0.3%) and 9.8% (95% CI 6.3%-13.3%), respectively. We observed a decreasing prevalence of late AMD after 2006, which became most prominent after age 70. Prevalences were similar for gender across all age groups except for late AMD in the oldest age category, and a trend was found showing a higher prevalence of CNV in Northern Europe. After 2006, fewer eyes and fewer ≥80-year-old subjects with CNV were visually impaired (P = 0.016). Projections of AMD showed an almost doubling of affected persons despite a decreasing prevalence. By 2040, the number of individuals in Europe with early AMD will range between 14.9 and 21.5 million, and for late AMD between 3.9 and 4.8 million. CONCLUSION: We observed a decreasing prevalence of AMD and an improvement in visual acuity in CNV occuring over the past 2 decades in Europe. Healthier lifestyles and implementation of anti-vascular endothelial growth factor treatment are the most likely explanations. Nevertheless, the numbers of affected subjects will increase considerably in the next 2 decades. AMD continues to remain a significant public health problem among Europeans.

Ethnicity-Based Differences in the Association of LOXL1 Polymorphisms with Pseudoexfoliation/Pseudoexfoliative Glaucoma: A Meta-Analysis.

Pseudoexfoliation (PEX) is an age-related disorder of the extracellular matrix; it is strongly associated with glaucoma, the leading cause of irreversible blindness worldwide. We conducted an ethnic-based meta-analysis of the association of LOXL1 polymorphisms with PEX/pseudoexfoliative glaucoma (PEXG). Association studies were retrieved systematically from PubMed, EMBASE, and Web of Knowledge. Allelic and genotype frequencies of rs3825942, rs1048661, and rs2165241 were compared between PEX/PEXG and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random effects model. Overall, 39 independent cohorts were included. Rs3825942 (G) was an at risk allele for PEX/PEXG in Caucasians, Japanese, Koreans, Chinese, South Asians, and Middle Easterners, but protective in Black South Africans (OR = 0.10, 95%CI:0.06-0.16). Rs1048661 (G) was an at risk allele for PEX/PEXG in Caucasians, South Asians, Middle Easterners and Black South Africans, but was protective in Japanese (OR = 0.03, 95%CI:0.02-0.06) and Koreans (OR = 0.10, 95%CI:0.05-0.22). These associations we-re confirmed for the genotypic recessive models. Rs2165241 (C) was a protective allele for PEX/PEXG in Caucasians, but was an at risk allele in Japanese (OR = 7.49, 95%CI:3.22-17.41) and Koreans (OR = 6.63, 95%CI:2.60-16.90). This was confirmed for the genotypic dominant model. Other genetic and/or environmental factors may modify the effect of LOXL1 polymorphisms in certain ethnic groups.

Increasing Prevalence of Myopia in Europe and the Impact of Education.

PURPOSE: To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend. DESIGN: Meta-analysis of population-based, cross-sectional studies from the European Eye Epidemiology (E(3)) Consortium. PARTICIPANTS: The E(3) Consortium is a collaborative network of epidemiological studies of common eye diseases in adults across Europe. Refractive data were available for 61 946 participants from 15 population-based studies performed between 1990 and 2013; participants had a range of median ages from 44 to 78 years. METHODS: Noncycloplegic refraction, year of birth, and highest educational level achieved were obtained for all participants. Myopia was defined as a mean spherical equivalent ≤-0.75 diopters. A random-effects meta-analysis of age-specific myopia prevalence was performed, with sequential analyses stratified by year of birth and highest level of educational attainment. MAIN OUTCOME MEASURES: Variation in age-specific myopia prevalence for differing years of birth and educational level. RESULTS: There was a significant cohort effect for increasing myopia prevalence across more recent birth decades; age-standardized myopia prevalence increased from 17.8% (95% confidence interval [CI], 17.6-18.1) to 23.5% (95% CI, 23.2-23.7) in those born between 1910 and 1939 compared with 1940 and 1979 (P = 0.03). Education was significantly associated with myopia; for those completing primary, secondary, and higher education, the age-standardized prevalences were 25.4% (CI, 25.0-25.8), 29.1% (CI, 28.8-29.5), and 36.6% (CI, 36.1-37.2), respectively. Although more recent birth cohorts were more educated, this did not fully explain the cohort effect. Compared with the reference risk of participants born in the 1920s with only primary education, higher education or being born in the 1960s doubled the myopia prevalence ratio-2.43 (CI, 1.26-4.17) and 2.62 (CI, 1.31-5.00), respectively-whereas individuals born in the 1960s and completing higher education had approximately 4 times the reference risk: a prevalence ratio of 3.76 (CI, 2.21-6.57). CONCLUSIONS: Myopia is becoming more common in Europe; although education levels have increased and are associated with myopia, higher education seems to be an additive rather than explanatory factor. Increasing levels of myopia carry significant clinical and economic implications, with more people at risk of the sight-threatening complications associated with high myopia.

Prevalence of refractive error in Europe: the European Eye Epidemiology (E(3)) Consortium.

To estimate the prevalence of refractive error in adults across Europe. Refractive data (mean spherical equivalent) collected between 1990 and 2013 from fifteen population-based cohort and cross-sectional studies of the European Eye Epidemiology (E(3)) Consortium were combined in a random effects meta-analysis stratified by 5-year age intervals and gender. Participants were excluded if they were identified as having had cataract surgery, retinal detachment, refractive surgery or other factors that might influence refraction. Estimates of refractive error prevalence were obtained including the following classifications: myopia ≤-0.75 diopters (D), high myopia ≤-6D, hyperopia ≥1D and astigmatism ≥1D. Meta-analysis of refractive error was performed for 61,946 individuals from fifteen studies with median age ranging from 44 to 81 and minimal ethnic variation (98 % European ancestry). The age-standardised prevalences (using the 2010 European Standard Population, limited to those ≥25 and <90 years old) were: myopia 30.6 % [95 % confidence interval (CI) 30.4-30.9], high myopia 2.7 % (95 % CI 2.69-2.73), hyperopia 25.2 % (95 % CI 25.0-25.4) and astigmatism 23.9 % (95 % CI 23.7-24.1). Age-specific estimates revealed a high prevalence of myopia in younger participants [47.2 % (CI 41.8-52.5) in 25-29 years-olds]. Refractive error affects just over a half of European adults. The greatest burden of refractive error is due to myopia, with high prevalence rates in young adults. Using the 2010 European population estimates, we estimate there are 227.2 million people with myopia across Europe.

Update on pseudoexfoliation syndrome pathogenesis and associations with intraocular pressure, glaucoma and systemic diseases.

PURPOSE OF REVIEW: Pseudoexfoliation (PEX) syndrome is a common age-related disorder affecting intraocular and extraocular tissues. This review focuses on recent publications related with the pathogenesis and associations of PEX syndrome with intraocular pressure (IOP), glaucoma and systemic diseases. RECENT FINDINGS: In PEX tissues, expression of lysyl oxidase-like 1 (LOXL1) was found to be markedly dysregulated. This may adversely affect elastin metabolism and lead to elastotic alteration in tissues such as lamina cribrosa. There is increasing evidence that cellular stress conditions and low-grade chronic inflammatory processes are involved in the pathogenesis of PEX. Although there is an increased risk for glaucoma development in patients with PEX and ocular hypertension as compared with non-PEX patients with ocular hypertension, LOXL1 single nucleotide polymorphisms were not associated with intraocular pressure (IOP) differences. Lack of association of PEX with all-cause mortality or dementia has been reported recently. The association with vascular diseases is not consistent among different studies. SUMMARY: Despite the high prevalence of the LOXL1 variants in the general population, a much lower proportion of the population develops PEX, suggesting that in addition to LOXL1, other genetic, epigenetic and environmental factors may contribute to the development of PEX. Also, LOXL1 cannot help to identify those with PEX at increased risk for glaucoma development. Increased risk for glaucoma development in PEX patients who present with increased IOP may be related to other factors beyond IOP, contributing to increased vulnerability of the optic nerve to glaucoma development in the presence of PEX.

Safety and Efficacy of Prostaglandin Analogues in the Immediate Postoperative Period after Uneventful Phacoemulsification.

Prostaglandin analogues (PGAs) have been associated with the development of pseudophakic macular edema (PME) in complicated cataract cases, but evidence on their effects in uncomplicated phacoemulsification remains controversial. This two-arm, prospective, randomised study included patients with glaucoma or ocular hypertension under PGA monotherapy who were scheduled for cataract surgery. The first group continued PGA use (PGA-on), while the second discontinued PGAs for the first postoperative month and reinitiated use afterwards (PGA-off). Topical non-steroidal anti-inflammatory drugs (NSAIDs) were routinely administered to all patients during the first postoperative month. The patients were followed up for three months and the primary outcome was PME development. Secondary outcomes were corrected distance visual acuity (CDVA), central and average macular thickness (CMT and AMT), and intraocular pressure (IOP). The analysis included 22 eyes in the PGA-on group and 33 eyes in the PGA-off group. No patient developed PME. CDVA was not significantly different between the two groups (p = 0.83). CMT and AMT showed a small but statistically significant increase until the end of follow-up (p < 0.001). Mean IOP values had no significant differences between the groups at each visit (p > 0.05). At the end of follow-up, the IOP values were significantly lower than baseline in both groups (p < 0.001). In conclusion, PGA administration with concomitant topical NSAIDs appears to be a safe practice in the early postoperative period of uncomplicated phacoemulsification.

Comparison of two protocols of diode laser transscleral cyclophotocoagulation in refractory glaucoma.

INTRODUCTION: Diode laser transscleral cyclophotocoagulation (DLTSCPC) remains the most commonly used cyclodestructive procedure. Nonetheless, there is no common consensus on a standardized technique. METHODS: In this prospective randomized pilot study we compare the "pop"-titrated and "slow-burn" DLTSCPC techniques for a follow-up period of 3 months. The major outcomes of this study were intraocular pressure (IOP) before and after the procedure and the incidence of adverse events. Furthermore, postoperative pain, postoperative intraocular inflammation and corrected distance visual acuity (CDVA) were evaluated. RESULTS: Mean baseline IOP decreased from 37.9 ± 12.7 mmHg in the pop group and 41.2 ± 9.6 mmHg in the slow-burn group to 20.3 ± 13.9 mmHg and 21.3 ± 13.4 mmHg at the final follow-up visit, corresponding to a 45.8 ± 31.7% and 46.3 ± 32.6% reduction respectively. 64.3% and 57.1% of patients had IOP ≥6 and≤ 21 mmHg in the pop and slow-burn groups respectively. The occurrence of adverse events was similar in both groups, with 1 case of hyphema in the pop group and 2 cases in the slow-burn group, and 1 case of hypotony in each group. Mean CDVA remained unchanged until the end of follow-up from 2.05 ± 0.84 to 2.04 ± 0.8 logMAR in the pop group and from 1.93 ± 0.78 to 1.89 ± 0.7 logMAR in the slow-burn group. Nonetheless, 4 eyes in each group encountered CDVA loss. Postoperative pain and inflammation were also similar between groups. DISCUSSION: At the 3rd postoperative month, safety and efficacy was similar in the two techniques. The relative ease of the slow-burn technique may make its application more appealing to ophthalmic surgeons beyond glaucoma specialists.

Ocular Surface Disease Signs and Symptoms in Patients with Pseudoexfoliative Glaucoma: A Case-Control Study.

PURPOSE: The present study evaluates the differences in the prevalence of the signs and symptoms of ocular surface disease (OSD) in patients with PEX glaucoma (PEXG), compared to other glaucoma types (non-PEXG). METHODS: Patients with non-PEXG and PEXG were prospectively examined for the presence and severity of OSD signs and questioned for symptoms using the OSDI (ocular surface disease index) questionnaire. RESULTS: 116 patients were prospectively enrolled (58 non-PEXG and 58 PEXG). PEXG subjects who were older, had lower central corneal thickness (CCT) values, at a more advanced glaucoma stage and required more IOP lowering drops. OSD signs were prevalent in both groups: conjunctival hyperemia (74.5% non-PEXG vs. 94.8% PEXG), eyelid redness (70.7% vs. 96.6%), conjunctival (74.1% vs. 93.1%) and corneal fluorescein staining (81% vs. 93.1%) and abnormal TFBUT (82.8% vs. 87.9%). When adjusted for potential confounders, (older age, thinner CCT, more advanced glaucoma in PEXG) eyelid redness remained the only parameter significantly associated with PEXG, being 11 times more likely to occur in this group (p = 0.037). CONCLUSION: Subjects with PEXG presented a higher frequency of signs of OSD compared to other glaucoma types. When accounting for confounding factors, the only difference between the groups was the significantly higher presence (11 times more likely) of eyelid redness in PEXG, suggesting, in addition to glaucoma treatment, the impact of PEX on ocular surface integrity.

Ocular parameter changes after phacoemulsification in pseudoexfoliative eyes: case-control study.

PURPOSE: To assess changes of angle morphometric parameters, anterior chamber depth (ACD), intraocular pressure (IOP), and endothelial cell density (ECD) after uneventful phacoemulsification in eyes with pseudoexfoliation syndrome (PEX) compared with those in eyes without PEX and to evaluate the effect of these changes on effective lens position and postoperative refraction. SETTING: Papageorgiou Hospital, Thessaloniki, Greece. DESIGN: Prospective case-control study. METHODS: Angle opening distance, trabecular-iris space area, and scleral spur angle width were measured using anterior segment optical coherence tomography. ACD was assessed using IOLMaster and ECD using specular microscopy. All parameters were evaluated at baseline and 2 months postoperatively. RESULTS: 42 patients (42 eyes) with PEX and 39 patients (39 eyes) without PEX who underwent uneventful phacoemulsification were enrolled. All angle parameters and ACD increased significantly after phacoemulsification in both groups ( P < .001), with no statistically significant difference between them ( P > .05). Percentile change in ACD was greater in PEX eyes ( P = .017). Regarding the mean refractive prediction error, no statistically significant differences were found between the study groups ( P = .68). A statistically significant trend toward hyperopic shift was noted in the PEX group ( P = .039). IOP and ECD diminished postoperatively in both groups, with no statistically significant difference between the study groups ( P = .09 and P = .22, respectively). CONCLUSIONS: PEX, compared with non-PEX eyes, demonstrated a greater anterior chamber deepening and a hyperopic shift after phacoemulsification. These could be related to the zonular laxity in eyes with PEX and imply that PEX eyes may require a modified target refraction to achieve the desired refractive outcome.

Association Between Dietary Salt Intake and Open Angle Glaucoma in the Thessaloniki Eye Study.

PRCIS: In the Thessaloniki Eye Study (TES) incidence phase population, frequent dietary salt intake was potentially associated with increased risk of open angle glaucoma in antihypertensive users. PURPOSE: The aim was to examine the association between dietary salt intake and glaucoma by antihypertensive use in the TES population. MATERIALS AND METHODS: The study population included TES incidence phase participants. Dietary salt intake frequency was assessed by self-report. Outcomes included prevalence of any open angle glaucoma (OAG), primary open angle glaucoma (POAG), and pseudoexfoliation (PEX). Covariates included demographics, cardiovascular disease, migraines, diabetes, steroid use, smoking, history of cataract surgery, central corneal thickness, intraocular pressure, blood pressure, and antihypertensive use. Logistic regression was used to examine associations between frequency of salt intake and glaucoma, controlling for covariates and stratified by antihypertensive use. RESULTS: The study included 1076 participants 80.5±4.4 years old, of whom 518 were female. There were 89/1076 (8.3%) participants with any OAG, 46/789 (5.8%) with POAG, and 287/1030 (27.9%) with PEX. In participants with antihypertensive use, frequent versus never salt intake was associated with increased risk of any OAG [adjusted odds ratio (aOR)=2.65, 95% confidence interval (CI)=1.12, 6.28; n=784] and POAG (aOR=3.59, 95% CI=1.16, 11.11; n=578) overall, and additionally in participants with diastolic blood pressure <90 mm Hg (aOR=2.42, 95% CI=1.00, 5.84; n=735) for OAG. There were no statistically significant adjusted associations between salt intake and PEX, or in participants without antihypertensive use. CONCLUSIONS: In TES participants assessed for OAG in the prevalence and incidence phases, frequent salt intake may be associated with increased OAG in those who take antihypertensive medication. Further investigation is needed of salt intake and glaucoma in hypertensive individuals.

Treatment of spontaneous corneal perforation secondary to undiagnosed Sjögren's syndrome using regenerating agent and autologous serum eye drops.

PURPOSE: The aim of this study was to report a case of sterile corneal ulcer leading to perforation, which was treated effectively with autologous serum eye drops, topical regenerative agent (poly-carboxymethylglucose sulfate), steroids, and systemic immunosuppression in a patient with undiagnosed primary Sjögren's syndrome. METHODS: A 74-year-old female presented with a month's history of gradually worsening blurry vision in her left eye. Ophthalmic examination revealed a central descemetocele with excessive corneal stromal melting and absence of signs of infection. A bandage contact lens was applied for tectonic support along with topical corticosteroid and antibiotic drops. Autoimmune screen disclosed a diagnosis of Sjögren's syndrome, and the patient was commenced on systemic immunosuppression. Forty-eight hours after presentation, the patient developed a localized corneal perforation, presenting with a flat anterior chamber. RESULTS: Urgent amniotic membrane transplantation was arranged while topical dexamethasone, moxifloxacin, and autologous serum eye drops were administered. After 24 h of intensive topical treatment, a significant reforming of the anterior chamber and subsequent gradual regeneration of the corneal stroma were noted, thus postponing amniotic grafting. The patient remained under close monitoring, showing progressive clinical improvement. Regenerating agent eye drops (Cacicol20®) were also applied over the next month, with careful and slow tapering of topical dexamethasone. Further improvement of corneal thickness was observed, and visual acuity increased to 20/80. CONCLUSION: This case report demonstrates the successful medical treatment of an autoimmune-related sterile corneal perforation without surgical intervention, highlighting the fact that early diagnosis and rigorous medical treatment with autologous serum and regenerating agent eye drops can effectively aid tissue regeneration and favorable visual rehabilitation.

Peripapillary Choroidal Neovascular Membrane Secondary to Sarcoidosis-Related Panuveitis: Treatment with Aflibercept and Ranibizumab with a 50-month Follow-Up.

A case of peripapillary choroidal neovascular membrane (PCNM) secondary to sarcoidosis-related panuveitis successfully treated with anti-vascular endothelial growth factor (anti-VEGF) agents and systemic immunomodulatory therapy is reported. Diagnosis and follow-up were based on fundoscopic, optical coherence tomography as well as fluorescein angiography findings. A 45-year-old female patient presented with sudden onset bilateral blurring of vision. Fundoscopy revealed bilateral granulomatous panuveitis with solitary peripheral granuloma in the right eye and PCNM in the left eye. Diagnostic work-up including conjunctival biopsy confirmed the diagnosis of sarcoidosis. Topical and systemic corticosteroids controlled the inflammation. Within 4 weeks, PCNM showed rapid enlargement (best-corrected visual acuity [BCVA]: 6/60) with foveal involvement. Monthly intravitreal aflibercept injections and systemic methotrexate were administered. After 5 aflibercept injections, anatomical and functional improvement was noted (BCVA: 6/6). Due to aflibercept unavailability, further treatment included ranibizumab injections. During a 50-month follow-up period, every anti-VEGF injection was followed by total NV regression and 6/6 BCVA. Both aflibercept and ranibizumab appear to be effective in the treatment of PCNM secondary to sarcoidosis.

Twelve-Year Incidence of Open-angle Glaucoma: The Thessaloniki Eye Study.

OBJECTIVE: The objective of this study was to determine the 12-year incidence of open-angle glaucoma (OAG), with further classification into primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEXG), in an elderly White population. DESIGN: A longitudinal, population-based study in urban Northern Greece. PARTICIPANT: Surviving cohort of the 2554 Thessaloniki Eye Study subjects 60 years and above who had the baseline examination. METHODS: The surviving cohort was re-examined 12 years after baseline, using the same methodology and the same standard operating procedures as in the baseline examination. The definitions of glaucoma and pseudoexfoliation were consistent throughout the study. The 12-year incidences of OAG, POAG, and PEXG with corresponding 95% confidence intervals (CIs) were calculated for the whole study population, consisting of clinic-visit and home-visit participants. The population at risk was defined as those who did not meet the study criteria for the diagnosis of glaucoma in either eye at baseline. MAIN OUTCOME MEASURES: Twelve-year incidence of OAG, with further classification into POAG and PEXG. RESULTS: Of 1468 eligible subjects in the surviving cohort, 1092 were examined (participation rate 74%). Mean age at baseline was 68.9±4.6 years. Mean follow-up time was 11.6±1.6 years. The 12-year incidence of OAG was 4.4% (95% CI: 3.3-5.8); 0.37% per year. In the overall population the incidence of POAG and PEXG was 2.1% (95% CI: 1.3-3.2) and 2.3% (95% CI: 1.5-3.4), respectively. The corresponding incidence proportions were 2.9 (95% CI: 1.8-4.3) in those without PEX and 8.9 (95% CI: 5.8-12.9) in those with PEX at baseline and/or incidence. The latter was strongly associated with higher odds for incident glaucoma (odds ratio=3.34, 95% CI: 1.83-6.08, P<0.001). Of all incident OAG cases, 11.1% (95% CI: 4.4-24) had baseline intraocular pressure >21 mm Hg. CONCLUSIONS: The incidence of OAG was similar or higher compared with other White populations. The incidence of glaucoma in those with PEX was higher compared with the incidence of glaucoma in those without PEX.

Factors associated with non-active retinal capillary density as measured with Confocal Scanning Laser Doppler Flowmetry in an elderly population: the Thessaloniki Eye Study (TES).

PURPOSE: To identify factors associated with retinal capillary density as measured with Confocal Scanning Laser Doppler Flowmetry (Heidelberg retina flowmeter (HRF)) in the Thessaloniki Eye Study (TES). METHODS: Participants of the TES (age ≥60 years, cross-sectional population-based study) were assessed for active capillary density in the superior and inferior peripapillary retina using the HRF. Pixel-by-pixel analysis was performed to quantify the percentage of zero flow pixels (ZFPs; surrogate for % retinal area with non-active capillaries). Multivariable regression analyses were performed to assess the association of non-active vascular density with ophthalmic and systemic variables. Glaucoma, late age-related macular degeneration and diabetic retinopathy subjects were excluded. RESULTS: 1189 subjects were included in the analysis. Older age (per year) was associated with higher percentage of ZFP in both the superior (slope estimate (SE)=0.0020) and the inferior (SE=0.0019) peripapillary retina (p<0.0001). History of migraine was associated with lower percentage of ZFP (SE=-0.0166) compared with no history of migraine in the superior peripapillary retina only (p<0.05). Higher intraocular pressure ((IOP) per mm Hg) and height (per cm) were associated with higher percentage of ZFP in the inferior peripapillary retina only (SE=0.0012, p<0.05 and SE=0.0005, p<0.05, respectively). The group consuming vegetables one to three times per week compared with the group consuming vegetables at least once a day had higher percentage of ZFP only in the inferior peripapillary retina (SE=0.0080, p<0.05). CONCLUSION: At a population level, our study revealed associations of older age, higher IOP and taller height with lower active retinal capillary density and of migraine with higher capillary density. Looking further into these associations may provide insight into disease mechanisms.

Factors Associated With Retinal Vessel Diameters in an Elderly Population: the Thessaloniki Eye Study.

Purpose: To identify the factors associated with retinal vessel diameters in the population of the Thessaloniki Eye Study. Methods: Cross-sectional population-based study (age ≥ 60 years). Subjects with glaucoma, late age-related macular degeneration, and diabetic retinopathy were excluded from the analyses. Retinal vessel diameters were measured using the IVAN software, and measurements were summarized to central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole to venule ratio (AVR). Results: The analysis included 1614 subjects. The hypertensive group showed lower values of CRAE (P = 0.033) and AVR (P = 0.0351) compared to the normal blood pressure (BP) group. On the contrary, the group having normal BP under antihypertensive treatment did not have different values compared to the normal BP group. Diastolic BP (per mm Hg) was negatively associated with CRAE (P < 0.0001) and AVR (P < 0.0001), while systolic BP (per mm Hg) was positively associated with CRAE (P = 0.001) and AVR (P = 0.0096). Other factors significantly associated included age, sex, alcohol, smoking, cardiovascular disease history, ophthalmic medication, weight, and IOP; differences were observed in a stratified analysis based on BP medication use. Conclusions: Our study confirms previous reports about the association of age and BP with vessel diameters. The negative correlation between BP and CRAE seems to be guided by the effect of diastolic BP as higher systolic BP is independently associated with higher values of CRAE. The association of BP status with retinal vessel diameters is determined by diastolic BP status in our population. Multiple other factors are also independently associated with retinal vessel diameters.

Factors associated with undiagnosed open-angle glaucoma: the Thessaloniki Eye Study.

PURPOSE: To identify factors associated with undiagnosed open-angle glaucoma (OAG), primary open-angle glaucoma (POAG), and pseudoexfoliative glaucoma (PEXG) in an elderly population in Thessaloniki, Greece. DESIGN: Cross-sectional population-based study. METHODS: Randomly selected subjects > or =60 years (n = 2,554) participated in the study. Subjects were classified as having POAG or PEXG according to specific criteria and using a two-scale definition of glaucoma. Undiagnosed glaucoma was defined as absence of either prior diagnosis of glaucoma or ocular hypertension or prior medical treatment for glaucoma or prior glaucoma surgery. Logistic regression analyses were performed with age, gender, family history of glaucoma, history of cataract surgery, visual acuity, vertical cup-to-disk (C/D) ratio, intraocular pressure, Advanced Glaucoma Intervention Study visual field score, time since last eye doctor visit, and type of OAG as covariates. RESULTS: The prevalence of undiagnosed glaucoma was 57.1% (56/98) for POAG, significantly higher than the prevalence of 34.9% (15/43) for PEXG (P = .017). POAG patients presented three to four times increased risk to be undiagnosed compared with PEXG patients (P = .02 and P = .04, respectively). Patients with OAG who had not visited an ophthalmologist during the last year had six times an increased risk to be undiagnosed (P = .003). In POAG, smaller vertical C/D ratio was statistically significantly associated with an increased risk to be undiagnosed (P = .008). CONCLUSIONS: Lack of regular visits to an ophthalmologist was a major factor for undiagnosed OAG. POAG was more likely to be undiagnosed than PEXG. Since C/D ratio was associated with undiagnosed POAG, standardized protocols involving thorough evaluation of the optic disk are recommended for ophthalmologists.

Investigational drugs targeting prostaglandin receptors for the treatment of glaucoma.

INTRODUCTION: Prostaglandin F2α analogs were the first prostaglandin agonists introduced for glaucoma treatment. Thanks to their efficacy and favorable tolerability they set a high bar in competition, with a resultant paucity in new hypotensive drug development for many years. However, the scientific community has shown recently a new interest in exploring new options for glaucoma treatment, generating a remarkable incentive in the marketplace for new drugs. AREAS COVERED: This article reviews agents targeting prostaglandin receptors that are currently being investigated for glaucoma treatment. We searched published literature for agonists targeting all subtypes of prostaglandin receptors found in ocular tissues. EP and FP receptor agonists are currently in the spotlight of clinical research, while less attention is paid in DP receptor agonists. EXPERT OPINION: Prostaglandin analogs, targeting different and combinations of receptor subtypes and compounds that exhibit additivity to commonly prescribed medications seem to be highly promising options. New treatments need to be safe, more effective, superior to existing therapies, tolerable and cost-effective. New generation compounds with multiple mechanisms of action or multiagent formulations are vigorously being investigated and generated in laboratories around the world.

Tolerable rates of visual field progression in a population-based sample of patients with glaucoma.

AIMS: To provide population-based data on the maximum tolerable rate of progression to avoid visual impairment (maxTRoP_VI) and blindness (maxTRoP_BL) from open-angle glaucoma (OAG). METHODS: Participants with OAG in the Thessaloniki Eye Study (cross-sectional, population-based study in a European population) were included in the analysis. Visual impairment was defined as mean deviation (MD) equal to or worse than -12dB and blindness as MD equal to or worse than -24dB. Additional thresholds for visual impairment were tested. For each participant maxTRoP_VI was defined as the rate of progression which would not lead to visual impairment during expected lifetime. MaxTRoP_BL was defined accordingly. Both parameters were calculated for each OAG subject using age, sex, MD and life expectancy data. The eye with the better MD per subject was included in the analysis. RESULTS: Among 135 subjects with OAG, 123 had reliable visual fields and were included in the analysis. The mean age was 73±6 years and the median MD was -3.65±5.28dB. Among those, 69.1% would have a maxTRoP_VI slower than -1dB/year and 18.7% would have a maxTRoP_VI between -1 and -2dB/year. Also, 72.4% would have a maxTRoP_BL slower than -2dB/year. For all tested thresholds for visual impairment, approximately 86% of the OAG study participants would not be able to tolerate a rate of progression equal to or faster than -2dB/year. CONCLUSIONS: The majority of patients with glaucoma in our study would have a maximum tolerable rate of progression slower than -1dB/year in their better eye. Patient-tailored strategies to monitor the visual field are important, but raise the issue of feasibility with regard to the number of visual field tests needed.

Risk factors for Age-related Macular Degeneration in a Greek population: The Thessaloniki Eye Study.

PURPOSE: To assess the association of potential risk factors with early and late age-related macular degeneration (AMD) in the Thessaloniki Eye Study (TES) population Design: Population-based, cross-sectional study of subjects over age of 60 living in Thessaloniki, Greece Methods: Subjects without any AMD features and subjects with early and late AMD (neovascular AMD or geographic atrophy) were identified in the TES cohort using standardized procedures and masked grading of stereo color fundus photos. Demographic, lifestyle, systemic and other ophthalmic covariates were also collected during a detailed examination process. Their association with AMD was investigated using univariate and multivariate adjusted logistic regression models. RESULTS: Among the 2108 participants with gradable photos, the grading process identified 1204 subjects with no AMD, 848 subjects with early AMD, and 56 subjects with late AMD (24 with geographic atrophy and 32 with neovascular AMD). In multivariate analysis, compared to no AMD, late AMD was positively associated with older age (OR:1.16; 95%CI:1.10-1.22 per year of age), current smoking (smoking vs. never smoking, OR:2.34; 95%CI:1.12-4.90), prior cataract surgery (cataract surgery vs. no cataract surgery OR:2.06; 95%CI:0.96-4.40), marital status (divorced/separated vs. married, OR:3.10; 95%CI:1.08-8.93) and with 60% lower odds when sleeping in the afternoon (yes vs. no, OR:0.40; 95%CI:0.22-0.72). Early AMD was positively associated with older age (OR: 1.03; 95%CI:1.01-1.05 per year of age) and negatively with higher pulse pressure (OR:0.99; 95%CI:0.98-0.99 per mmHg). CONCLUSIONS: In TES, apart for well-known risk factors for AMD like age, smoking, and cataract surgery, two novel behavioral risk factors for prevalent late AMD were suggested. Sleeping in the afternoon was associated with 60% decreased odds for late AMD and 67% decreased odds for neovascular AMD. Being divorced/separated compared to married was associated with 3-fold higher odds for late AMD. Large longitudinal population-based studies will be necessary to further establish the potential late AMD risk effects of these two novel factors, to demonstrate potential implications of underlying pathogenetic mechanisms, and to explore preventive measures and therapeutic targets.

Overdiagnosis of open-angle glaucoma in the general population: the Thessaloniki Eye Study.

PURPOSE: To assess the overdiagnosis of open-angle glaucoma (OAG) and to investigate associated factors. METHODS: This was a cross-sectional, population-based study of an urban Caucasian population in northern Greece. Randomly selected subjects ≥60 years (n = 2554) participated in the Thessaloniki Eye Study. The definition of OAG required the presence of structural and functional damage, irrespective of intraocular pressure (IOP). Non-OAG subjects were classified as overdiagnosed with OAG if they had reported at least one of the following (self-reported glaucoma): (i) prior diagnosis of glaucoma, (ii) prior laser for glaucoma, (iii) prior glaucoma surgery. Factors associated with the overdiagnosis of OAG were investigated using a logistic regression model. RESULTS: Of 57 (2.2%) subjects with self-reported glaucoma, 34 (60%) were overdiagnosed with OAG, corresponding to a prevalence of 1.3% (34/2554). In a logistic regression model among non-OAG subjects, worse visual acuity (VA) (20/200 or worse versus 20/25 or better; odds ratio (OR) = 4.30, 95% Confidence Intervals (CI), 1.13-16.35), family history of glaucoma (OR = 8.69, 95% CI, 2.83-26.67) and history of cataract surgery (OR = 11.50, 95% CI, 3.85-34.36) were statistically significantly associated with the overdiagnosis of OAG. Age, sex, higher IOP, higher vertical cup-to-disc ratio and pseudoexfoliation were not statistically significant. CONCLUSION: The overdiagnosis of OAG was substantial in this elderly, Caucasian population. The overdiagnosis of glaucoma has not been previously addressed in population-based studies and needs to be further explored.