Prevalence of Myopic Macular Features in Dutch Individuals of European Ancestry With High Myopia.

IMPORTANCE: High myopia incidence and prevalence is increasing worldwide, and the visual burden caused by myopia is expected to rise accordingly. Studies investigating the occurrence of myopic complications in individuals of European ancestry with high myopia are scarce, hampering insights into the frequency of myopic retinal complications in European individuals and their visual burden. OBJECTIVE: To assess the frequency of myopic macular features in individuals of European ancestry with high myopia. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis of the Dutch Myopia Study (MYST) and individuals with high myopia from the Rotterdam Study (RS) included 626 patients with high myopia (spherical equivalent of refractive error [SER] ≤-6 diopters [D] or axial length [AL] ≥26 mm) who underwent an extensive ophthalmic examination including multimodal retinal imaging. In addition to this combination of a population-based cohort study and mix-based high myopia study, a systematic literature review was also performed to compare findings with studies of individuals of Asian ancestry. EXPOSURES: High myopia, age, and AL. MAIN OUTCOMES AND MEASURES: Frequency of myopic macular and optic disc features: tessellated fundus, myopic macular degeneration (MMD), staphyloma, peripapillary intrachoroidal cavitation, peripapillary atrophy (PPA), and "plus" lesions (choroidal neovascularization, Fuchs spot, and lacquer cracks). RESULTS: The mean (SD) SER of the combined study population (MYST and RS) was -9.9 (3.2) D; the mean (SD) age was 51.4 (15.1) years, and 387 (61.8%) were women. The prevalence of MMD was 25.9% and increased with older age (P for trend <.001), lower SER (odds ratio [OR], 0.70; 95% CI, 0.65-0.76; P < .001), and higher AL (OR, 2.53; 95% CI, 2.13-3.06; P < .001). Choroidal neovascularization or Fuchs spot was present in 2.7% (n = 17), both lesions in 0.3% (n = 2), and lacquer cracks in 1.4% (n = 9). Staphyloma, PPA, and MMD were highly prevalent in visual impaired and blind eyes (frequency was 73.9% [20 of 27], 90.5% [19 of 21], and 63.0% [17 of 27] of unilateral blind eyes for MMD, staphyloma, and PPA, respectively). Seven previous studies in Asian populations reported a variable MMD frequency ranging from 8.3% to 64%, but frequencies were similar for comparable risk profiles based on age and SER. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of a highly myopic Dutch population of European ancestry, myopic retinal features were frequent; were associated with age, SER, and AL; and occurred in all visually severely impaired eyes. The absence of treatment options for most of these retinal complications emphasizes the need for effective strategies to prevent high myopia.

Phenotypic Consequences of the GJD2 Risk Genotype in Myopia Development.

Purpose: To study the relatively high effect of the refractive error gene GJD2 in human myopia, and to assess its relationship with refractive error, ocular biometry and lifestyle in various age groups. Methods: The population-based Rotterdam Study (RS), high myopia case-control study MYopia STudy, and the birth-cohort study Generation R were included in this study. Spherical equivalent (SER), axial length (AL), axial length/corneal radius (AL/CR), vitreous depth (VD), and anterior chamber depth (ACD) were measured using standard ophthalmologic procedures. Biometric measurements were compared between GJD2 (rs524952) genotype groups; education and environmental risk score (ERS) were calculated to estimate gene-environment interaction effects, using the Synergy index (SI). Results: RS adults carrying two risk alleles had a lower SER and longer AL, ACD and VD (AA versus TT, 0.23D vs. 0.70D; 23.79 mm vs. 23.52 mm; 2.72 mm vs. 2.65 mm; 16.12 mm vs. 15.87 mm; all P < 0.001). Children carrying two risk alleles had larger AL/CR at ages 6 and 9 years (2.88 vs. 2.87 and 3.00 vs. 2.96; all P < 0.001). Education and ERS both negatively influenced myopia and the biometric outcomes, but gene-environment interactions did not reach statistical significance (SI 1.25 [95% confidence interval {CI}, 0.85-1.85] and 1.17 [95% CI, 0.55-2.50] in adults and children). Conclusions: The elongation of the eye caused by the GJD2 risk genotype follows a dose-response pattern already visible at the age of 6 years. These early effects are an example of how a common myopia gene may drive myopia.

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.

Association of Axial Length With Risk of Uncorrectable Visual Impairment for Europeans With Myopia.

IMPORTANCE: Myopia (ie, nearsightedness) is becoming the most common eye disorder to cause blindness in younger persons in many parts of the world. Visual impairment due to myopia is associated with structural changes of the retina and the globe because of elongation of the eye axis. How axial length-a sum of the anterior chamber depth, lens thickness, and vitreous chamber depth-and myopia relate to the development of visual impairment over time is unknown. OBJECTIVES: To evaluate the association between axial length, spherical equivalent, and the risk of visual impairment and to make projections of visual impairment for regions with high prevalence rates. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study uses population-based data from the Rotterdam Study I (1990 to 1993), II (2000 to 2002), and III (2006 to 2008) and the Erasmus Rucphen Family Study (2002 to 2005) as well as case-control data from the Myopia Study (2010 to 2012) from the Netherlands. In total, 15 404 individuals with data on spherical equivalent and 9074 individuals with data on axial length were included in the study; right eyes were used for analyses. Data were analyzed from September 2014 to May 2016. MAIN OUTCOMES AND MEASURES: Visual impairment and blindness (defined according to the World Health Organization criteria as a visual acuity less than 0.3) and predicted rates of visual impairment specifically for persons with myopia. RESULTS: Of the 15 693 individuals included in this study, the mean (SD) age was 61.3 (11.4) years, and 8961 (57.1%) were female. Axial length ranged from 15.3 to 37.8 mm; 819 individuals had an axial length of 26 mm or greater. Spherical equivalent ranged from -25 to +14 diopters; 796 persons had high myopia (ie, a spherical equivalent of -6 diopters or less). The prevalence of visual impairment varied from 1.0% to 4.1% in the population-based studies, was 5.4% in the Myopia Study, and was 0.3% in controls. The prevalence of visual impairment rose with increasing axial length and spherical equivalent, with a cumulative incidence (SE) of visual impairment of 3.8% (1.3) for participants aged 75 years with an axial length of 24 to less than 26 mm and greater than 90% (8.1) with an axial length of 30 mm or greater. The cumulative risk (SE) of visual impairment was 5.7% (1.3) for participants aged 60 years and 39% (4.9) for those aged 75 years with a spherical equivalent of -6 diopters or less. Projections of these data suggest that visual impairment will increase 7- to 13-fold by 2055 in high-risk areas. CONCLUSIONS AND RELEVANCE: This study demonstrated that visual impairment is associated with axial length and spherical equivalent and may be unavoidable at the most extreme values in this population. Developing strategies to prevent the development of myopia and its complications could help to avoid an increase of visual impairment in the working-age population.

Clinical presentation and morbidity of contact lens-associated microbial keratitis: a retrospective study.

PURPOSE: To investigate the clinical presentation, isolated organism, treatment, and morbidity of contact lens-associated microbial keratitis needing hospitalization. METHODS: This retrospective study included all consecutive patients with contact lens-associated microbial keratitis hospitalized in the Rotterdam Eye Hospital from January 1, 2005, to December 31, 2009. All data regarding epidemiological characteristics, clinical presentation, isolated organism, and treatment were collected from medical records. RESULTS: There were 109 cases (108 patients) of contact lens-associated microbial keratitis hospitalized during the study period. Mean age was 33.3 ± 15.4 (SD) years. Pseudomonas aeruginosa was the most frequently isolated microorganism (68.8 %), with minor resistance to gentamicin (2.7 %) and ofloxacin (1.3 %). At time of presentation, best corrected visual acuity (BCVA) was very poor, with the largest proportion of patients (65.1 %) seeing worse than 0.05 Snellen. After intensive treatment, the visual outcome improved considerably, with the largest proportion (67.0 %) achieving a BCVA ≥ 0.7 Snellen. Low BCVA at admission was significantly associated with a worse final BCVA. A total of 22 patients (20.2 %) required corneal transplantation (three emergency cases). Larger size of stromal infiltrate was significantly associated with the need for corneal transplantation. CONCLUSION: Microbial keratitis is a serious complication of contact lens wear, with approximately one out of five hospitalized cases requiring corneal transplantation. Ofloxacin, or a combination of gentamicin and cephazolin, still appear to be excellent first-choice therapies in the Netherlands, as little resistance has developed to these antibiotics.

Five-year follow-up on the effect of oral acyclovir after penetrating keratoplasty for herpetic keratitis.

PURPOSE: To investigate the long-term effect of oral acyclovir administered during the first 6 months after penetrating keratoplasty (PK) for herpetic eye disease (HED). METHODS: A 5-year follow-up was undertaken for a patient population from a placebo-controlled, randomized trial on acyclovir prophylaxis after keratoplasty. In this former study the effectiveness of oral acyclovir prophylaxis was significant during the first 2 years after keratoplasty. Prospective data such as graft survival, graft clarity, vascularization, infective events, and rejection episodes were obtained from the national keratoplasty follow-up registry. Additional clinical data were derived from the medical charts. RESULTS: For 47 of the original 63 enrolled patients, the 5-year follow-up was completed. Comparing the acyclovir group with the placebo group, we found that with regard to the cumulative clinically evident recurrences, there was a statistically significant lower monthly event rate in the acyclovir group (P = 0.037). There were no statistically significant differences in visual acuity or in the use of oral aciclovir between the two treatment groups. The incidences of graft failure, vascularization, and medication or surgery for glaucoma were too low to analyze differences between the two groups. CONCLUSION: The results of our study suggest that oral acyclovir prescribed during the first 6 months after PK for HED protects against clinically evident HED recurrences during the first 5 years following PK.

Incidence of rigid gas-permeable contact lens wear after keratoplasty for keratoconus.

PURPOSE: To review retrospectively the charts of all 190 patients who underwent penetrating keratoplasty for keratoconus in one hospital during a 5-year period (1995-2000), with special attention paid to contact lens fitting. METHODS: The frequency of postoperative contact lens use, the time to fit lenses after grafting, tolerance and visual acuity, and postoperative risks for the graft were studied. RESULTS: The authors successfully fitted large-diameter (12 mm) tricurve rigid gas-permeable contact lenses for 90 (47%) of 190 penetrating keratoplasty patients with good tolerance. There were nine dropouts, and 91 eyes were corrected in another way. Fitting contact lenses after grafting usually started after 8.5 months (range, 1-60 months). The average tolerance was 9.2 hours a day (range, 2-12 hours), and best-corrected visual acuity was 20/25 (range, 20/16-20/200). The average follow-up was at least half a year. The average age of the patient at the first lens fitting was 36.2 years (range, 14-75 years). There was no increased risk in graft rejection. CONCLUSIONS: Twelve-millimeter rigid gas-permeable contact lens wear was successful in 47% of patients who underwent penetrating keratoplasty for keratoconus. It does not interfere with the use of chronic postoperative topical medication, nor does it increase the risk of corneal graft rejection. It is necessary to recommend likely use of contact lenses to patients who have undergone grafting surgery.

Comparison of complication rates and postoperative astigmatism between nylon and mersilene sutures for corneal transplants in patients with Fuchs endothelial dystrophy.

PURPOSE: The purpose of this study is to evaluate corneal astigmatism and suture-related complications for transplants sutured with nylon and transplants sutured with Mersilene in primary corneal transplants for Fuchs endothelial dystrophy. METHODS: A retrospective, observational, and comparative study between transplants sutured with either nylon 10-0 or 11-0 (n = 108) or Mersilene 11-0 (n = 58) was done. One hundred sixty-six eyes of 140 patients who received a primary penetrating keratoplasty for Fuchs endothelial dystrophy between 1995 and 2001 at the Rotterdam Eye Hospital in Netherlands were included. RESULTS: Overall, transplant survival did not differ between groups (log-rank test; P = 0.24). During the first 2 years after transplantation, significantly lower astigmatism was seen in transplants sutured with nylon (P = 0.03). Transplants sutured with Mersilene had a significantly higher risk of surgical intervention to correct astigmatism or wound dehiscence after transplantation (hazard ratio, 2.83; 95% confidence interval, 1.34-6.01). Time to first infiltrate, metaplasia (marked scarring along the sutures), or cheesewiring was significantly less in the Mersilene group (P < 0.01). There was a tendency toward a higher risk of complications associated with loose or broken sutures in the nylon group (hazard ratio, 2.00; 95% confidence interval, 0.57-6.98), which was more pronounced after 2 years. CONCLUSIONS: During the first years after corneal transplant surgery, Mersilene sutures are associated with a higher risk of complications and more interventions to correct suture-related problems. However, after 2 years, the grafts seem to be able to retain Mersilene sutures with less risk of suture-related complications as compared with grafts with retained nylon sutures. These favorable long-term effects of Mersilene sutures may outweigh its short-term disadvantage in patients with Fuchs endothelial dystrophy.

Effect of oral acyclovir after penetrating keratoplasty for herpetic keratitis: a placebo-controlled multicenter trial.

OBJECTIVE: To determine the prophylactic effect of oral acyclovir on the recurrence rate of herpetic eye disease after penetrating keratoplasty. DESIGN: A randomized, double-masked, placebo-controlled multicenter trial. PARTICIPANTS: Sixty-eight consecutive patients (68 eyes) with corneal opacities due to herpetic eye disease who underwent penetrating keratoplasty. INTERVENTION: Oral acyclovir 400 mg twice daily or placebo tablets for 6 months. MAIN OUTCOME MEASURES: The recurrence rate of herpetic eye disease-related events and rejection episodes, proven by viral cell culture or polymerase chain reaction. RESULTS: During the 2-year follow-up period, there were 3 culture-proven herpetic eye disease recurrences in the acyclovir group and 9 in the placebo group. Lifetime survival analysis of the probability of remaining free from recurrence revealed a significantly reduced risk of recurrent herpetic disease in the acyclovir-treated group. CONCLUSION: This study suggests that oral acyclovir effectively prevents herpes-related recurrences after penetrating keratoplasty in herpetic eye disease.

Clinical and theoretical results of intraocular lens power calculation for cataract surgery after photorefractive keratectomy for myopia.

OBJECTIVES: To describe the refractive results of cataract surgery after photorefractive keratectomy (PRK) for patients with myopia, and to find a more accurate method to predict intraocular lens (IOL) power in these cases. DESIGN: Nonrandomized, retrospective clinical study. PATIENTS AND METHODS: Nine patients (15 eyes) who underwent cataract surgery after prior PRK to correct myopia were identified. The medical records of both the laser and cataract surgery centers were reviewed. MAIN OUTCOME MEASURES: Eight different keratometric values (K values; measured or calculated) were entered into 3 different IOL calculation formulas: SRK/T, Holladay 1, and Hoffer Q. The actual biometry and IOL parameters were used to predict postoperative refraction, which was compared with the actual refractive outcome. Also, the relative underestimation of the refractive change in corneal dioptric power by keratometry after PRK was calculated. RESULTS: In 7 of 15 eyes, IOL exchange or piggybacking was performed because of hyperopia. Retrospectively, the most accurate K value for IOL calculation was found to be the pre-PRK K value corrected by the spectacle plane change in refraction. Use of the Hoffer Q formula would have avoided postoperative hyperopia in more cases than the other formulas. The mean underestimation of the change in corneal power after PRK varied from 42% to 74%, depending on the method of calculation. CONCLUSION: The predictability of IOL calculation for cataract surgery after PRK can be improved by using a corrected, refraction-derived K value instead of the measured, preoperative K value.

Recovery of the visual acuity in a family with Reis-Bückler dystrophy.

BACKGROUND: The hereditary Reis-Bückler dystrophy is one of the anterior localised corneal dystrophies with superficial reticulated opacities, sometimes in combination with recurrent attacks of corneal erosion. Phototherapeutic keratectomy (PTK) is now the first method to consider for managing this disease when intervention is required. METHODS: We treated six eyes of four related patients with Reis-Bückler dystrophy, who had a demonstrable reduction in visual acuity due to corneal opacities within their virgin corneas (three eyes), penetrating (one eye) or lamellar (two eyes) grafts. We present the results of change in visual acuity and best corrected spherical spectacle and contact lens refraction at 1 year following surgery. In one case, we had to fit a rigid contact lens to correct the hyperopic shift which caused anisometropia. RESULTS: The mean spherical refractive change 1 year after PTK surgery was 0.33+/-S.D., 1.8D. A hyperopic shift was observed in four eyes. Visual acuity remained stable in all patients 1 year after surgery. The central corneal area remained clear, and mean best spectacle corrected visual acuity improved from +0.8 logMAR before PTK to +0.15 logMAR after 1 year. There was no significant change (P>0.8) between the mean 1 year best spectacle corrected visual acuity (+0.125 log MAR +/- S.D. 0.15) and the best contact lens corrected visual acuity (+0.108 log MAR +/- S.D. 0.16). After fitting a contact lens in one patient to correct anisometropia, the hyperopic shift did not change significantly during 12 months of follow-up. It was not necessary to adjust the lens parameters. One patient required cataract surgery. CONCLUSION: PTK corneal surgery is the treatment of first choice when intervention is required in patients with Reis-Bückler dystrophy because it is safe and much less invasive than lamellar or penetrating keratoplasty. Contact lens fitting following PTK has not changed corneal shape.