VOLUME 82 - ISSUE 6

Purpose: The underlying genetic causes of keratoconus are essentially unknown. Here, we conducted whole-exome sequencing in 2 Brazilian families with keratoconus.
Methods: Whole-exome sequencing was performed on 6 keratoconus-affected individuals of 2 unrelated pedigrees from Southern Brazil. Pathogenic variants were identified in a modified Trio analysis (1 parent and 2 children) using candidate gene filtering. All the affected subjects underwent detailed corneal tomographic evaluation. Clinically relevant variants that were present in affected individuals at minor allele frequencies <1% were examined in the 1000 Genomes Project single nucleotide polymorphism ABraOM and transcription gene (RefSeq and Ensembl) databases.
Results: In family 1, a sequence variant in chromosome 1 (q21.3) was observed within the filaggrin gene. All the tested family members shared a heterozygous missense pathogenic variant in the c.4678C>T position. In family 2, exome analysis demonstrated a sequence variant in chromosome 16 (q24.2) within the gene encoding zinc finger protein 469 (ZNF469). Members of family 2 shared a heterozygous missense variant in the c.1489G>A position. In addition, the exomes of the 2 families were examined for shared genetic variants among all affected individuals. Filtering criteria did not identify any rare sequence variants in a single gene segregated in both families.
Conclusion: Our findings show that a complete genotype-phenotype correlation could not be identified, suggesting that keratoconus is a genetically heterogeneous disease. In addition, we believe that whole-exome sequencing-based segregation analysis is probably not the best strategy for identifying variants in families with isolated keratoconus.

Keywords: Keratoconus; Cornea; Whole-exome sequencing; Sequence analysis; Ectasia

Purpose: To analyze the outcomes of in-the-bag toric intraocular lens implantation for anterior capsular tears during phacoemulsification.
Methods: The cohort of this retrospective, consecutive, interventional case series included eight patients. One patient was excluded as the tear was used to enlarge the rhexis. The mean preoperative astigmatism was -1.67D (± 0.98) and the mean preoperative unaided logMAR visual acuity was 0.62 (± 0.76). The mean angle between the anterior capsule tear and the closest intraocular lens haptic was 51.25° (range, 30°-90°).
Results: The final unaided logMAR visual acuity was 0.16 (± 0.21) and the final cylinder was -1.1 D (± 0.59). The mean follow-up duration was about 2 ± 1.2 months. In this case series, no lens had to be explanted or rotated postoperatively. Placement of a toric intraocular lens in the presence anterior capsule tear was safe in all patients. An angle of at least 30° remained between the tear and the intraocular lens haptic.
Conclusion: Placement of toric intraocular lens in the presence of an anterior capsule tear may be safe, at least in cases with a 30° angle between the anterior capsule tear and the intraocular lens haptic.

Keywords: Phacoemulsification/adverse effects; Cataract; Lens implantation, intraocular; Visual acuity

Purpose: To evaluate the impact of visual acuity, visual field damage, and other factors on the quality of life in Brazilian patients with glaucoma.
Methods: This cross-sectional prospective study involved 49 patients with glaucoma enrolled based on the presence of reproducible standard automated perimetry defects in at least one eye at the time of evaluation. A detailed ophthalmologic examination was performed on each patient. All patients had reproducible standard automated perimetry and completed an NEI VFQ-25 questionnaire. The associations of the quality of life scores to the best-corrected visual acuity and the visual field loss of the better and worse eyes were investigated.
Results: The mean quality of life score of the patients was 58.8 ± 18.7 units. The highest and lowest mean values (85.0 ± 24.2 and 37.5 ± 36.5 units) were observed in the “Social Functioning Subscale” and “Driving Subscale,” respectively. Patients with advanced glaucoma (mean deviation <-12 dB) in the worse eye had significantly lower quality of life scores (p=0.007). There was a significant correlation between the quality of life scores and the visual acuity of the better and worse eyes (r²=13%, p=0.010 and r²=32%, p<0.001, respectively). There was also a significant correlation between the quality of life scores and standard automated perimetry mean deviation of the better and worse eyes (r²=13%, p=0.023 and r²=47%, p<0.001, respectively). In a multivariate model containing socioeconomic and comorbidity indices, quality of life remained significantly related to the standard automated perimetry mean deviation of the better and worse eyes (r²=23%, p=0.29 and r²=49%, p<0.001, respectively) as well as to the visual acuity of the better and worse eyes (r²=18%, p=0.017 and r²=40%, p<0.001, respectively).
Conclusion: The standard automated perimetry mean deviation and the visual acuity of the better and worse eyes were associated with lower quality of life in Brazilian patients with glaucoma. Quality of life was mostly highly associated with the standard automated perimetry mean deviation of the worse eye.

Keywords: Glaucoma; Eye health; Quality of life; Visual field; Surveys and questionnaires/standards; Visual acuity

Purpose: To evaluate the biocompatibility of three-dimensional (3D) printed orbital spheres for evisceration.
Materials: A total of 10 consecutive patients (eight females and two males; mean age, 46.8 ± 14.2 years) underwent evisceration of blind painful eyes. 3D spherical implants produced by a rapid prototype machine were used to restore orbital volume. The implants were produced from a commercially available photocurable resin (Fullcure^®). Systemic toxicity was evaluated by comparing serum biochemical measurements (creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase, albumin, creatinine, urea, alkaline phosphatase, and C-reactive protein) before and at 12 months after surgery. Local toxicity was assessed by the evaluation of signs of socket inflammation at the first postoperative month. Changes in implant size were determined by computed tomography scans at 2 and 12 months after surgery.
Results: The postoperative evaluations were uneventful. The biochemical evaluation showed no significant changes after surgery. None of the patients presented signs of orbital implant inflammation, infection, exposure, or extrusion. Computed tomography scan evaluations revealed no changes in implant size.
Conclusion: To the best of our knowledge, this is the first phase-1 clinical study to certify the biocompatibility of the Fullcure resin for orbital implants in humans. The 3D printing technology permits fast and accurate production of implants for this purpose.

Keywords: Orbit evisceration; Orbital diseases/rehabilitation; Orbit/surgery; Printing, three-dimensional; Acrylic resins/therapeutic use; Biocompatible materials; Orbital implants

Purposes: To evaluate the sensitivity, specificity, and cutoff points for the ROPScore, which is based on cumulative risk factors for the prediction of retinopathy of prematurity (ROP), in a population of very low birth weight (BW) preterm infants in southern Brazil.
Methods: The medical records of all preterm infants with a very low birth weight ≤1,500 g and/or gestational age ≤32 weeks screened for retinopathy of prematurity in two Brazilian institutions between August 2009 and December 2015 were retrospectively reviewed. ROPScores were calculated using birth weight and gestational age, the use of oxygen therapy with mechanical ventilation, and weight gain proportional to birth weight, as measured at postpartum week six and the need for blood transfusions.
Results: The study cohort included 322 infants with a mean birth weight of 1181.8 ± 292.5 g and mean gestational age of 29.5 ± 2.3 weeks. The incidences of any stage of retinopathy of prematurity and severe retinopathy of prematurity were 68.3% and 17%, respectively. ROPScore values ranged from 8.7 to 19.9. The best cutoff point for sensitivity and specificity was 11 for any stage of retinopathy of prematurity and 14.5 for severe retinopathy of prematurity. For any stage of retinopathy of prematurity, the sensitivity and specificity of the ROPScores were 98.6% (95% confidence interval = 97.9%-99.3%) and 35.3% (95% confidence interval= 32.3%-38.3%), with a positive predictive value of 76.6% (95% confidence interval= 74.0%-79.2%) and a negative predictive value of 92.3% (95% confidence interval= 90.6%-94.0%). For severe retinopathy of prematurity, the sensitivity was 100% and specificity was 57.3% (95% confidence interval= 54.2%-60.4%), with positive predictive value of 22% (95% confidence interval= 19.4%-24.6%) and negative predictive value of 100%. The cutoff points correctly identified all infants that developed severe retinopathy of prematurity in this cohort.
Conclusions: The ROPScore was useful to identify preterm babies at risk for retinopathy of prematurity. In this population, the ROPScore detected all patients at risk for any stage retinopathy of prematurity and severe retinopathy of prematurity. The ROPScore values in this study were similar to those previously described, thereby successfully validating the ROPScore for early detection of retinopathy of prematurity in very low birth weight preterm infants.

Keywords: Infant, premature; Retinopathy of prematurity; Very low birth weight; Risk factors; ROPScore; Severity of illness index; Blindness

PURPOSE: The aim of this study was to determine the functional and anatomical success rates as well as the safety of sutureless combined surgery involving vitreous base removal and internal limiting membrane peeling after Brilliant Blue G (0.5 mg/mL) staining for the management of idiopathic macular holes after three years.
METHODS: Forty-six eyes of 46 patients with an idiopathic macular hole were enrolled in this retrospective study. The inclusion criteria were macular holes with a minimum linear diameter below 1,500 mm, 0.05 or better decimal best-corrected visual acuity and duration of symptoms less than two years. The exclusion criteria included pregnancy, optic nerve atrophy, advanced glaucoma, and other chronic ocular diseases. The surgical procedure included internal limiting membrane peeling after Brilliant Blue G (0.5 mg/mL) staining, along with C₃F₈ tamponade and face-down positioning for three days postoperatively. Ophthalmologic examinations and optical coherence tomography were performed at 1 and 7 days and 1, 6, 12, 24, and 36 months postoperatively. If no anatomic closure of the macular holes occurred within the first month, the area of the internal limiting membrane peeling was enlarged in a second procedure. Multiple logistic regression and chi-squared tests were used for data analyses, and p-values of <0.05 were considered significant.
RESULTS: Out of 46 eyes with a preoperative idiopathic macular hole, anatomic closure was achieved in 42 (91.3%) after one procedure and in 45 (97.8%) after an additional surgery. The median postoperative best-corrected visual acuity improvement was 0.378 (range: 0.050-0.900) decimal. None of the patients experienced macular hole reopening, surgery-related complications, or ocular complications related to the dye.
CONCLUSION: Combined surgery including vitreous base removal and internal limiting membrane peeling after staining with Brilliant Blue G (0.5 mg/mL) for the management of idiopathic macular holes resulted in adequate staining, best-corrected visual acuity improvement, and macular hole closure with no signs of ocular toxicity at the three-year follow-up examination.

Keywords: Vitrectomy/methods; Macular hole; Coring agents; Rosaniline dyes; Brilliant blue

Purpose: This report addresses refractive, topographic, visual acuity, and optical coherence tomography outcomes 12 months after femtosecond, laser-assisted insertion of Ferrara intrastromal corneal ring segments in keratoconic eyes at a depth of 60%.
Methods: Interventional, prospective, non-comparative case series. We performed femtosecond, laser-assisted insertion of Ferrara intrastromal corneal ring segments in 15 keratoconic eyes. We included patients with documented keratoconus who voluntarily signed informed consents if they had best spectacle-corrected visual acuity ≥0.30 logMAR and corneal thickness ≥400 µm. We excluded patients with previous ocular surgery or corneal curvatures >65 diopters (D). Our main outcome measures were best spectacle-corrected visual acuity and corneal topographic parameters (flattest, steepest and average keratometry [K]), evaluated at baseline and at 1-,3-,6-, and 12-month follow-ups.
Results: The mean ± standard deviation baseline uncorrected visual acuity and best spectacle-corrected visual acuity were 1.03 ± 0.46 and 0.42 ± 0.13, respectively; the 12-month mean standard deviation uncorrected visual acuity and best spectacle-corrected visual acuity were 0.72 ± 0.37 and 0.31 ± 0.16, respectively, without significant differences (p=0.05 for both). The mean best spectacle-corrected visual acuity improvements were statistically significant after 3- (p=0.02) and after 6-months (p=0.02). The mean baseline flattest (K1), steepest (K2), and overall keratometries (mean power) were 48.35 ± 3.65 D, 53.67 ± 3.38 D, and 50.84 ± 3.36 D, respectively. The 12-month mean ± standard deviations for flattest-K1, steepest-K2, and overall K were 46.53 ± 3.70 D, 49.83 ± 3.50 D, and 48.12 ± 3.49 D respectively, with statistically significant differences for all three topographic parameters (p=0.01).
Conclusions: Ferrara intrastromal corneal ring segment insertions at a depth of 60% yield satisfactory visual, refractive, and keratometric results in keratoconic eyes.

Keywords: Cornea/pathology; Corneal diseases; Keratoconus; Corneal surgery, laser

Purpose: To assess the relationship between pseudoexfoliation syndrome and incidence of complications and related clinical factors in patients undergoing cataract surgery.
Methods: We conducted a retrospective cohort study of 503 of 551 patients who underwent phacoemulsification surgery over 2 years in a health care district in Northwest Spain. In total, 120 of 681 eyes undergoing the procedure had pseudoexfoliation syndrome. Data on the surgical procedure and associated complications were extracted from the medical record. Complications included any combination of posterior capsular rupture, vitreous loss, zonular dialysis, and nuclear or lens luxation.
Results: We found a significant association between pseudoexfoliation syndrome and zonular dialysis (odds ratio [OR], 6.89; 95% CI, 2.27-20.93), intraoperative miosis (OR, 2.15; 95% CI, 1.10-4.22), and lens luxation >1.5 mm (OR, 9.49; 95% CI, 0.85-105.54). However, when adjusting for the overall risk of complications in pseudoexfoliation syndrome patients in consideration of myopia, use of anticoagulants or α-agonists, previous mydriasis, and anterior chamber length, the OR decreased to 1.02 (95% CI, 0.47-2.21) and was therefore not significant.
Conclusion: Zonular dialysis and intraoperative miosis were intraoperative complications in cataract surgery patients with pseudoexfoliation syndrome when compared to controls.

Keywords: Exfoliation syndrome; Phacoemulsification; Cataract extraction/adverse effects

PURPOSE: To investigate the potential associations between keratoconus and catalase rs1001179, superoxide dismutase 2 rs4880, and glutathione peroxidase 1 rs1050450 gene polymorphisms in a Turkish population.
METHODS: The study group included 121 unrelated keratoconus patients and 94 unrelated healthy controls. Blood samples (200 ml) were collected from all patients and controls to isolate genomic DNA. Genotyping was performed to identify rs1001179, rs4880, and rs1050450 using real-time polymerase chain reaction (PCR). Genotype and allele frequencies were calculated; their associations with keratoconus risk were assayed, and the association with keratoconus risk and demographic factors was examined.
RESULTS: Glutathione peroxidase 1 rs1050450 polymorphism was present in 41% cases compared with 29% controls (OR=1.66; 95% CI=1.11-2.50; p=0.014). No association was observed between catalase rs1001179 and SOD2 rs4880 polymorphisms and keratoconus (for all, p>0.05).
CONCLUSIONS: This study evaluated possible relationships between rs1050450, rs1001179, and rs4880 polymorphisms and keratoconus susceptibility. We found a possible association between glutathione peroxidase 1 rs1050450 polymorphism and an increased risk of keratoconus. However, the genotype and allele frequencies were identical in the catalase rs1001179 and superoxide dismutase 2 rs4880 polymorphisms. Further studies are needed to analyze the effect of such variations in identifying keratoconus susceptibility.

Keywords: Keratoconus; Glutathione peroxidase; Catalase; Superoxide dismutase; Polymorphism, genetic

Purpose: The aim of this study was to evaluate anterior segment parameters and corneal aberrations in patients with retinitis pigmentosa using Scheimpflug imaging and to compare the findings with those for healthy controls.
Methods: This single-center, case-control study included patients diagnosed with retinitis pigmentosa who were followed up at the Department of Ophthalmology of Kayseri Training and Research Hospital between February and June 2018. Age- and sex-matched healthy individuals with no known ophthalmologic disease formed the control group. Both patients with retinitis pigmentosa and controls underwent comprehensive ophthalmic assessments, including the measurement of the best-corrected visual acuity calculation of the spherical equivalent, slit-lamp examination, stereoscopic fundus examination, computerized visual field test, and electroretinography. Topographic and aberrometric values were measured using Scheimpflug-based tomography.
Results: This study was performed on 52 eyes of 26 patients with retinitis pigmentosa (14 men) and 52 eyes of 26 healthy controls (11 men). The average keratometry (K_avg) values for the patient and control groups were similar (43.87 ± 2.23 versus 43.61 ± 1.68; p=0.546), but the maximum keratometry (K_max) value was significantly higher in the patient group (45.85 ± 2.35 and 44.69 ± 1.86; p=0.015). Patients with retinitis pigmentosa had a significantly lower central corneal thickness (518.5 ± 42.3 versus 534.1 ± 24.5, respectively; p=0.042) and maximal corneal thickness (509.1 ± 50.5 versus 530.5 ± 24.1, respectively; p=0.015). Additionally, the iridocorneal angle for the patients was significantly lower (31.6 ± 9.2 versus 35.9 ± 7.7, p=0.025). The aberrometric findings indicated that patients with retinitis pigmentosa had significantly more higher-order aberrations than those in the healthy controls (0.794 ± 51 and 0.398 ± 08, respectively; p<0.001).
Conclusions: The results of the present study demonstrated that patients with retinitis pigmentosa have different anterior segment parameters and corneal aberrations compared to healthy controls. These results should be supported by further studies.

Keywords: Retinitis pigmentosa; Anterior eye segment; Corneal topography; Aberrometry

Facial filler injection for soft-tissue augmentation, wrinkle reduction, and rejuvenation has recently become increasingly popular. This procedure is well accepted and widely performed because of its safety and excellent outcomes. However, complications may occur even in the most skilled hands. A 36-year-old female presented with immediate loss of vision in her right eye following the periocular injection of cosmetic hyaluronic acid facial filler into the glabellar region. The visual loss was accompanied by weakness of her left arm. Blindness may complicate cosmetic facial filler injection. The treating physician should have a firm knowledge of the facial vascular anatomy, and the patient should be aware of the potential blinding complications associated with facial filler injection.

Keywords: Dermal fillers; Hyaluronic acid; Injections; Cosmetic technique/adverse effects; Vision, low/etiology; Case reports

Ocular adnexal involvement in CD30+ lymphoproliferative disorders is rare. We report the case of a 73-year-old woman with a relapsing primary cutaneous anaplastic large cell lymphoma on her eyelid. A systemic extension study excluded extracutaneous involvement. Systemic chemotherapy resulted in an optimal response, with complete regression of the cutaneous lesions. There has been no recurrence during the 2 years of follow-up.

Keywords: Eyelid neoplasms; Lymphoma, primary cutaneous anaplastic large cell; Lymphoma, T-cell, cutaneous; Case reports

Vitreopapillary traction is an uncommon condition characterized by strong adhesion and the traction of the posterior hyaloid onto the optic disc and peripapillary retina, leading to optic disc elevation and visual loss. An 85-year-old man presented with a 6-month history of slow, progressive visual loss in the left eye along with optic disc edema. Swept-source optical coherence tomography B-scans revealed circumpapillary anterior-posterior persistent traction of dense vitreous strands onto the optic disc. Visual field examination demonstrated mild, generalized, diffuse sensitivity loss and blind-spot enlargement. A 25-gauge posterior vitrectomy was performed with posterior hyaloid separation from the optic disc, resulting in significant anatomical and visual improvement. In conclusion, swept-source optical coherence tomography aids in understanding the mechanism underlying visual loss in vitreopapillary traction. Moreover, posterior vitrectomy can effectively promote anatomical and visual improvements in these cases.

A 26-year-old woman presented at 28 weeks gestation with hypertensive choroidopathy associated with pre-eclampsia. Fundus photography, fundus autofluorescence, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography, and indocyanine green angiography were performed in both eyes in the immediate postoperative period. SD-OCT images were obtained before delivery and during a 3-month follow-up. Fundus autofluorescence exhibited patchy hyper- and hypoautofluorescent lesions; fluorescein and indocyanine green angiography revealed areas of choroidal ischemia; and SD-OCT showed disorganization of the outer retinal layers and disruption of the ellipsoid zone. After her blood pressure was stabilized, progressive recovery of the outer retinal layer was monitored on SD-OCT.

Keywords: Choroid diseases; Pre-eclampsia; Optical imaging; Tomography, optical coherence; Fluorescein angiography; Retinal photoreceptor cell outer segment; Blood-retinal barrier; Pregnancy; Case report

Pterygium pathogenesis has been mainly asso ciated with UV light exposure; however, this association remains quite controversial. The complete mechanism of pterygium also remains to be clarified. Factors such as inflammation, viral infection, oxidative stress, DNA methylation, inflammatory mediators, extracellular matrix modulators, apoptotic and oncogenic proteins, loss of heterozygosity, microsatellite instability, lymphangiogenesis, epithelial-mesenchymal cell transition, and alterations in cholesterol metabolism have been identified as causes. Several studies aimed to clarify the molecular mechanisms underlying the growth and proliferation of pterygium. Understanding its molecular basis provides new potential therapeutic targets for its prevention and treatment. A comprehensive search of the databases, namely, MedLine, EMBASE, and LILACS, was conducted with the following key words: pterygium, epidemiology, pathogenesis, biomarkers, and review. This review describes the epidemiology, clinical presentation, and current investigation of biological mediators involved in pterygium development.

Keywords: Pterygium/epidemiology; pathogenesis; Biomarkers; Review