Simple Technique for Stabilizing Toric Intraocular Lens during Removal of Ophthalmic Viscosurgical Device.

INTRODUCTION: The aim of this study was to describe a simple technique for the implantation of toric intraocular lenses (IOLs) with increased stability during ophthalmic viscosurgical device (OVD) removal. METHODS: The technique was performed on 20 eyes with 20 patients (mean age: 77.9 ± 9.21 years). The patients had cataract surgery with implantation of a single-piece, acrylic IOL (AcrySof Toric IOL, SN6A; Alcon Laboratories, Inc.). The intraoperative IOL rotation during OVD removal, rotational error of toric IOL axis at 30 min and 24 h after surgery, and mean preoperative and postoperative IOP were evaluated. Images were captured before and after removal of OVD from surgical video, and used to evaluate intraoperative IOL rotation. RESULTS: The mean amount of IOL rotation during OVD removal with the current technique was 0.88 ± 0.93°, which was less than the 10.25 ± 5.50° previously reported for the conventional technique. The rotational error of toric IOL axis at 30 min and 24 h were 3.90 ± 3.71 and 3.05 ± 3.22°, respectively. The mean preoperative IOP and postoperative IOP were 13.84 ± 2.39 and 14.15 ± 4.68 mm Hg, respectively. CONCLUSIONS: With the current technique, the toric IOL is stable during OVD removal and repositioning of the IOL during surgery is less likely to be required.

Effects of lighting environment on the degeneration of retinal ganglion cells in glutamate/aspartate transporter deficient mice, a mouse model of normal tension glaucoma.

Lighting conditions may affect the development of retinal degenerative diseases such as macular degeneration. In this study, to determine whether the lighting environment affects the progression of degeneration of retinal ganglion cells (RGCs), we examined glutamate/aspartate transporter (GLAST) heterozygous (GLAST+/-) mice, a mouse model of normal tension glaucoma. GLAST+/- mice were reared under a 12-h light-dark cycle (Light/Dark) or complete darkness (Dark/Dark) condition after birth. The total RGC number in the Dark/Dark group was significantly decreased compared with the Light/Dark group at 3 weeks old, while the number of osteopontin-positive αRGCs were similar in both groups. At 6 and 12 weeks old, the total RGC number were not significantly different in both conditions. In addition, the retinal function examined by multifocal electroretinogram were similar at 12 weeks old. These results suggest that lighting conditions may regulate the progression of RGC degeneration in some types of glaucoma.

Macular hole after Nd-YAG laser capsulotomy with OCT findings.

Patients with incomplete posterior vitreous detachment, especially with vitreomacular adhesion, can form a macular hole after Nd-YAG laser capsulotomy. It is recommended to inform the risk of forming a macular hole before Nd-YAG laser treatment.

Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye.

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.

Comparison of the Orientation of the Corneal Steep Meridian Determined by Image-Guided System and Manual Method in the Same Eye.

PURPOSE: To evaluate the difference between the preoperative marking methods for toric intraocular lens (IOL) implantations using an image-guided system (IGS) and the manual marking method in the same eye. PATIENTS AND METHODS: In this retrospective case series, 82 patients (101 eyes) who underwent cataract surgery using both manual and IGS (VERION, Alcon  Laboratories) marking were enrolled. First, preoperative reference marks were placed at 6 o'clock and 3 or 9 o'clock position under slit-lamp biomicroscope in the outpatient department using the manual method. Using the reference unit of IGS, the ocular surface data were captured and overlaid. The difference was then measured (preoperative axis misalignment). In the operating room, the orientation of the steep meridian of the manual method was determined based on this reference mark under the surgical microscope. Just before surgery, the digital degree gauge of IGS was overlaid on the ocular surface, and the difference was then measured (total axis misalignment). We calculated the intraoperative axis misalignment by subtracting preoperative axis misalignment from the total axis misalignment. RESULTS: Mean absolute preoperative, intraoperative, and total axis misalignment values were 3.87±3.95 degrees, 5.46±4.42 degrees, and 4.98±4.49 degrees, respectively. In preoperative, intraoperative, and total misalignment, the ratios of 10 degrees or greater were 10 (14.7%), 12 (17.6%), and 20 (19.8%) eyes, respectively. CONCLUSION: The manual method that determines the fixed position of the toric intraocular lens (IOL) may cause large misalignment compared with the IGS, suggesting that using manual method could sometimes result in a large misalignment of toric IOL implantation.

Incidence and Outcomes of Repositioning Surgery to Correct Misalignment of Toric Intraocular Lenses.

PURPOSE: To analyze the incidence and appropriate timing of repositioning surgery to correct misalignment of acrylic foldable toric intraocular lenses (IOLs). DESIGN: Retrospective, multicenter case series. PARTICIPANTS: Patients who had undergone phacoemulsification and implantation of toric IOL at 8 surgical sites. METHODS: Patient charts were reviewed to collect data on repositioning surgery of toric IOLs. MAIN OUTCOME MEASURES: Incidence, timing, and outcomes of repositioning surgery. RESULTS: Among 6431 eyes implanted with toric IOLs, 42 eyes (0.653%) of 42 patients underwent repositioning surgery at an average of 9.9±7.5 days (range, 0-30 days) after IOL implantation. The repositioning surgery significantly reduced misalignment from 32.9°±15.7° to 8.8°±9.7° (P < 0.001), which was measured at 7.6±5.0 weeks postoperatively. Refractive cylinder was significantly reduced from 2.4±1.1 diopters (D) to 1.1±0.8 D (P < 0.001). There was a significant negative correlation between the interval from cataract surgery to repositioning procedure and the degree of residual misalignment (r = -0.439, P < 0.001). The residual misalignment was 13.1°±13.5° when the repositioning surgery was performed within 6 days after cataract surgery, whereas the residual misalignment was 6.3°±5.9° when the IOL was repositioned 7 days or later (P < 0.001). In 2 eyes that were treated within 24 hours after cataract surgery, the IOL re-rotated significantly, and additional surgical intervention was required. CONCLUSIONS: Toric IOLs were repositioned in 0.653% of cases. A relationship was found between the timing of repositioning surgery and surgical outcome. These data suggest that repositioning surgery should be performed 1 week after IOL implantation.

A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.

Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: OR(A allele) = 9.87, P = 2.13 × 10(-217); non-Japanese: OR(A allele) = 0.49, P = 2.35 × 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.

Expression of vascular endothelial growth factor C in human pterygium.

Vascular endothelial growth factor C (VEGF-C) and its receptor VEGFR-3 mediate lymphangiogenesis. In this study, we analyzed the expression of VEGF-C and VEGFR-3 as well as lymphatic vessels in the pterygium and normal conjunctiva of humans. Fifteen primary nasal pterygia and three normal bulbar conjunctivas, surgically removed, were examined in this study. The lymphatic vessel density (LVD) and blood vessel density were determined by the immunolabeling of D2-40 and CD31, markers for lymphatic and blood vessels, respectively. VEGF-C and VEGFR-3 expression in pterygial and conjunctival tissue proteins was detected by Western blotting and were evaluated using immunohistochemistry. The LVD was significantly higher in the pterygium than normal conjunctiva (p < 0.05). Western blot demonstrated high-level expression of VEGF-C and VEGFR-3 in the pterygium compared with normal conjunctiva. VEGF-C immunoreactivity was detected in the cytoplasm of pterygial and normal conjunctival epithelial cells. The number of VEGF-C-immunopositive cells in pterygial epithelial cells was significantly higher than in normal conjunctival cells (p < 0.05). VEGFR-3 immunoreactivity was localized in the D2-40-positive lymphatic endothelial cells. The present findings suggest the potential role of VEGF-C in the pathogenesis and development of a pterygium through lymphangiogenesis and the VEGF-C/VEGFR-3 pathway as a novel therapeutic target for the human pterygium.

Ectopic cilia: a histopathological study.

Cilia are normally found at the eyelid margin, while ectopic cilia are one or more lash follicles appearing in an abnormal position within the eyelid. We herein report two cases of cilia located in the palpebral conjunctiva. A 31-year-old female and a 46-year-old male presented with ectopic cilia in the superior palpebral conjunctiva. Histopathological study of the excised ectopic cilia and related lesions showed the cilia-related lesion to be located in the epithelial pit that contains goblet cells, which is consistent with the crypts of Henle. The hair follicle was surrounded by granulation tissue, while a dermal papilla and a hair matrix, which are known to produce hair follicles, did not exist in the excised tissue. While anterior ectopic cilia are congenital, ectopic cilia in the palpebral conjunctiva may be acquired, and these aberrant cilia are associated with crypts of Henle and chronic inflammation.

Tissue factor expression in human pterygium.

PURPOSE: A pterygium shows tumor-like characteristics, such as proliferation, invasion, and epithelial-mesenchymal transition (EMT). Previous reports suggest that tissue factor (TF) expression is closely related to the EMT of tumor cells, and subsequent tumor development. In this study, we analyzed the expression and immunolocalization of TF in pterygial and normal conjunctival tissues of humans. METHODS: Eight pterygia and three normal bulbar conjunctivas, surgically removed, were used in this study. Formalin-fixed, paraffin-embedded tissues were submitted for immunohistochemical analysis with anti-TF antibody. Double staining immunohistochemistry was performed to assess TF and alpha-smooth muscle actin (α-SMA) or epidermal growth factor receptor (EGFR) expression in the pterygia. RESULTS: Immunoreactivity for TF was detected in all pterygial tissues examined. TF immunoreactivity was localized in the cytoplasm of basal, suprabasal, and superficial epithelial cells. The number of TF-immunopositive cells in pterygial epithelial cells was significantly higher than in normal conjunctival epithelial cells (p<0.001). TF immunoreactivity was detected in α-SMA-positive or -negative pterygial epithelial cells. EGFR immunoreactivity was detected in pterygial epithelium, which was colocalized with TF. CONCLUSIONS: These results suggest that TF plays a potential role in the pathogenesis and development of a pterygium, and that TF expression might be involved through EMT-dependent and -independent pathways.

Epidemiological and virological features of epidemic keratoconjunctivitis due to new human adenovirus type 54 in Japan.

BACKGROUND/AIMS: New human adenovirus (HAdV)-54 causes epidemic keratoconjunctivitis (EKC) and is virologically close to and has occasionally been detected as HAdV-8. Taking HAdV-54 into account, we re-determined HAdV type in EKC samples to determine its epidemiology in Japan, and examined the virological features of HAdV-54. METHODS: HAdV type was re-determined in 776 conjunctival swabs from Japan and 174 from six other countries, obtained between 2000 and 2009. Using 115 HAdV strains obtained before 1999, trends regarding HAdV-8 and HAdV-54 were also determined. In addition, immunochromatography (IC) kit features, DNA copy numbers and viral isolation of HAdV-54 in samples were evaluated. RESULTS: Recently, HAdV-37 and HAdV-54 have been the major causative types of EKC in Japan. HAdV-54 has been isolated each year since 1995, whereas HAdV-8 has become less common since 1997, although it remains the most common cause of EKC in the six other countries investigated where HAdV-54 is yet to be detected. HAdV-54 is comparable to other EKC-related HAdV types in terms of IC kit sensitivity and DNA copy numbers, although HAdV-54 grows more slowly on viral isolation. CONCLUSIONS: EKC due to HAdV-54 can result in epidemics; therefore, it should be accurately diagnosed and monitored as an emerging infection worldwide.