Characteristics of laterality in the optic nerve head microcirculation obtained by laser speckle flowgraphy in healthy subjects.

PURPOSE: To determine the characteristics of the laterality of the ocular microcirculation parameters obtained from laser speckle flowgraphy (LSFG) in the optic nerve head (ONH). SUBJECTS AND METHODS: We reanalyzed a total of 240 healthy subjects (169 men, 71 women) who had participated in a medical checkup program. We analyzed the average mean blur rate (MBR), maximum MBR (Max-MBR), minimum MBR (Min-MBR), and area ratio of the blood stream (ARBS). As the pulse waveform parameters, we also calculated the skew, blowout score (BOS), blowout time (BOT), rising rate, falling rate, flow acceleration index (FAI), acceleration time index (ATI), resistivity index (RI), and beat strength over MBR (BOM). All parameters were compared between left and right eyes. RESULTS: MBR-average, MBR-Max, MBR-Min, ARBS, skew, BOT, rising rate, falling rate, FAI, ATI, and ARBS did not differ significantly between the right and left eyes. The BOS in the right eyes was significantly lower than that of the left eyes, and the RI and BS in the right eyes were significantly higher than those of the left eyes. Similarly, for the whole of the ONH, the BOS in the tissue area (Tissue) and in the vessel area (Vessel) of the right eyes were significantly lower than those of the left eyes, and RI-Tissue, RI-Vessel, BOM-Tissue, and BOM-Vessel in the right eyes were significantly higher than those of the left eyes. CONCLUSION: By using LSFG, we observed laterality of the BOS, RI, and BOM, all of which are pulse wave form parameters in the ONH.

Loss of Down Syndrome Critical Region-1 Mediated-Hypercholesterolemia Accelerates Corneal Opacity Via Pathological Neovessel Formation.

OBJECTIVE: The calcineurin-NFAT (nuclear factor for activated T cells)-DSCR (Down syndrome critical region)-1 pathway plays a crucial role as the downstream effector of VEGF (vascular endothelial growth factor)-mediated tumor angiogenesis in endothelial cells. A role for DSCR-1 in different organ microenvironment such as the cornea and its role in ocular diseases is not well understood. Corneal changes can be indicators of various disease states and are easily detected through ocular examinations. Approach and Results: The presentation of a corneal arcus or a corneal opacity due to lipid deposition in the cornea often indicates hyperlipidemia and in most cases, hypercholesterolemia. Although the loss of Apo (apolipoprotein) E has been well characterized and is known to lead to elevated serum cholesterol levels, there are few corneal changes observed in ApoE-/- mice. In this study, we show that the combined loss of ApoE and DSCR-1 leads to a dramatic increase in serum cholesterol levels and severe corneal opacity with complete penetrance. The cornea is normally maintained in an avascular state; however, loss of Dscr-1 is sufficient to induce hyper-inflammatory and -oxidative condition, increased corneal neovascularization, and lymphangiogenesis. Furthermore, immunohistological analysis and genome-wide screening revealed that loss of Dscr-1 in mice triggers increased immune cell infiltration and upregulation of SDF (stromal derived factor)-1 and its receptor, CXCR4 (C-X-C motif chemokine ligand receptor-4), potentiating this signaling axis in the cornea, thereby contributing to pathological corneal angiogenesis and opacity. CONCLUSIONS: This study is the first demonstration of the critical role for the endogenous inhibitor of calcineurin, DSCR-1, and pathological corneal angiogenesis in hypercholesterolemia induced corneal opacity.

Characteristics and risk factors of recurrent keratoconus over the long term after penetrating keratoplasty.

PURPOSE: To determine the characteristics and risk factors of recurrent keratoconus (KC) after penetrating keratoplasty (PK). METHODS: We enrolled patients who had maintained clear grafts for at least 10 years after PK based on their medical records. Patients were divided into the KC group or Others group based on the primary indication for PK. Each case was reviewed for clinically observed corneal ectasia. Steepest keratometric power (Ks), cylinder (CYL), and difference between Ks and minimum keratometric power (MinK) were analyzed in patients that underwent corneal topography more than three times after the 5th postoperative year. RESULTS: One hundred one eyes of 82 patients were enrolled. The KC group comprised 50 eyes and the Others group comprised 51 eyes (herpes [n = 22], corneal leukoma [n = 12], and other [n = 17]). The mean period after PK was 27.2 years in the KC group and 26.0 years in the Others group. Recurrent KCs were observed in 18 eyes of 14 patients (36%), all of whom were in the KC group (p = 0.0001). Six of these eyes underwent PK again and all the grafts showed keratoconic changes histopathologically. The mean Ks during the whole observation period was 52.5 diopters (D) in the KC group and 49.2 D in the Others group (p < 0.0001). Logistic regression analysis revealed the risk factors of recurrent KC with positive Ks change and large CYL with significant p values (p = 0.0102, 0.0318, respectively). CONCLUSIONS: KC progresses even after PK over the long term, requiring re-grafting in some cases. Risk factors for recurrent KC after PK are increasing Ks over time and a large CYL.

Suppression of Allograft Rejection with Soluble VEGF Receptor 2 Chimeric Protein in a Mouse Model of Corneal Transplantation.

When a transparent cornea becomes opaque due to infectious diseases, trauma, or ophthalmic surgery, the impaired cornea is replaced with a donor cornea to improve visual function. In this corneal transplantation, the graft survival rate is comparatively high, partly because of lacking vascular and lymphatic vessel in cornea. However, the transplanted corneas sometimes become opaque if allograft rejection occurs. Suppression of allograft rejection is critical for favorable outcomes of corneal transplantation. The essential effects of endogenous monomeric soluble vascular endothelial growth factor receptors (VEGFRs) 1 and 2 have been reported in corneal angiogenesis and lymphangiogenesis. This study investigated the effects of dimeric soluble VEGFR2/Fc chimera protein on corneal allograft rejection for future clinical application. Allogeneic full-thickness corneal transplantation was performed in C57BL/6 to BALB/c mice. The recipients were treated by intrastromal injection of soluble VEGFR1/Fc chimera (sR1/Fc group), soluble VEGFR2/Fc chimera (sR2/Fc group), or human IgG1/Fc protein (IgG/Fc group) at 0, 7, and 14 days after surgery. Both hemangiogenesis and lymphangiogenesis were significantly suppressed in the corneas of the sR2/Fc group compared with the IgG/Fc group. All grafts failed due to corneal wound rupture in the sR1/Fc group. In the sR2/Fc group, respective donor-derived MHC class II(+)/CD11c(+) cells and CD11b-positive macrophage infiltration were reduced in the DLNs and the corneas showing a negative delayed-type hypersensitivity, compared with the IgG/Fc group. Our findings demonstrate that soluble VEGFR2/Fc chimera protein efficiently suppresses corneal allo-rejection, while reducing hemangiogenesis and lymhangiogenesis, and immune-competent cell-trafficking and may be a powerful tool for corneal allograft survival.

[To Protect Corneal Transparency against Diseases].

To protect corneal transparency, we tried to develop a new therapeutic strategy for corneal neovascularization, corneal scar, and TGFBI-related corneal dystrophy using nucleic acid drug. 1. The expression of angiopietin-like protein 2 (Angptl2) markedly increased in the neovascularized corneas compared to the normal cornea, and Angtpl2 was(a potent inducer of inflammatory corneal neovascularization. We have produced a single-stranded proline-modified short hairpin anti-Angptl2 ribonucleric acid interference (RNAi) molecule that is carried in a lipid nanoparticle for topical application. We have found this agent can penetrate all layers of the cornea. Angptl2 mRNA expression and corneal neovascularization were inhibited in a mouse alkari injury model by topical application of this agent. Thus, this modified RNAi agent is a new topical formulation for use against corneal neovascularization and scar. 2. Human umbilical vein endothelial cells (HUVECs) were cultured with human corneal keratocytes under serum-free conditions. We performed microarray gene-expression analysis in the coculture system and selected angiopoietin-like protein 7 (Angptl7). In vivo, intrastromal injections of an anti-Angptl7 RNAi agent into the avascular corneal stroma of mice resulted in the growth of blood vessels. Further, we examined the effects of Angptl7 on corneal nerves using culture rat trigeminal cells and this molecule had neurotrophic property on the cornea. Thus, Angpt17 is a unique molecule, which contain its bilateral character (anti-angiogenic and neurotrophic) in the cornea; an agonistic nucleic acid drug for Angptl7 may be a new therapeutic tool for protecting corneal transparency. 3. We examined local gene editing for TGFBI-related corneal dystrophy using CRISPR-Cas9 mediated homology directed repair (HDR). Cultured corneal keratocytes were obtained from a patient of R124H granular dystrophy. The R124H gene arrangement was corrected by a tranfection of guide RNA and HDR repair template single strand DNA in vitro. Thus, CRISPR-Cas9 medi-ated HDR could be a future radical treatment for TGFBI-related corneal dystrophy.

Investigation of the Sectorized Corneal Thickness of Eyes With Corneal Endothelial Dysfunction Using Anterior-Segment Optical Coherence Tomography.

PURPOSE: The aim of this study was to investigate the sectorized corneal thickness of eyes with corneal endothelial dysfunction using anterior-segment optical coherence tomography. METHODS: We retrospectively collected anterior-segment optical coherence tomography data conducted before endothelial keratoplasty on 53 eyes of 53 patients with corneal endothelial dysfunctions including Fuchs endothelial corneal dystrophy, bullous keratopathy (BK) after trabeculectomy, and BK after laser iridotomy and from 18 normal eyes of 18 subjects. The imaging points were divided into 17 sectors. The mean for each sector was calculated and compared with the corresponding superior/inferior and temporal/nasal sectors. RESULTS: In the normal eyes, the superior sectors were thicker than the inferior and the temporal sectors thinner than the nasal. In the diseased eyes, the superior sectors were thicker than the inferior in all subgroups; however, this tendency was no longer observed after the values were divided by the mean for the normal eyes. No significant differences were found on horizontal comparisons; however, after the values were divided by the mean for the normal eyes, the temporal sectors were thicker than the nasal. When comparing the values between the with-hole and the without-hole sides in the BK after laser iridotomy eyes, the sectors on the with-hole side were thicker than the other side. CONCLUSIONS: Corneal thickness of endothelial dysfunction was thicker in the superior sectors than the inferior but at a similar level to normal eyes. No significant differences were found for horizontal comparisons but, based on comparison with the normal eyes, the temporal sectors were thicker than the nasal.

Effects of corneal epithelial superficial keratectomy in patients with focal limbal stem cell disease.

PURPOSE: Irregular corneal epithelium in limbal stem cell disease can cause visual acuity to deteriorate substantially when it reaches the pupil. In this case series, we assessed the effectiveness of simple corneal epithelial superficial keratectomy in improving visual acuity in patients with irregular corneal epithelium in focal limbal stem cell disease covering the visual axis. OBSERVATIONS: We performed simple corneal epithelial superficial keratectomy in four patients (five eyes) with irregular corneal epithelium covering the visual axis. The main outcome measures were best-corrected visual acuity, slit lamp findings with fluorescein staining, anterior segment optical coherence tomography and histopathology. In all five eyes, slit lamp findings showed uneven fluorescein staining in a spiral pattern, with impaired corneal epithelial smoothness and visual disturbance. We removed the irregular epithelium in all five eyes. Visual acuity in all the eyes was improved immediately after surgery, and good visual acuity and stable epithelium were maintained for the duration of the observation periods. Hematoxylin and eosin staining showed, normal squamous and columnar epithelial cells. Goblet cells were not detected. CONCLUSIONSAND IMPORTANCE: Corneal epithelial superficial keratectomy can lead to a pathological diagnosis by examining the removed epithelial tissues, and result in excellent therapeutic outcomes in focal limbal stem cell disease reaching the pupil.

Three-year results of accelerated transepithelial cross-linking (30 mW/cm2 × 3 min) for keratoconus: a prospective study.

OBJECTIVE: To assess the long-term efficacy and safety of accelerated transepithelial corneal cross-linking (ATE-CXL) with 30 mW/cm2 × 3 min. METHODS AND ANALYSIS: Thirty-four eyes of 23 patients with progressive keratoconus (KCN) recruited within a single centre were enrolled in this prospective interventional study. Exclusion criteria included: history of Descemet's membrane rupture, glaucoma, uveitis, severe dry eye, concurrent corneal infections, and systemic disease that could affect corneal healing. ATE-CXL was performed with 3 min of ultraviolet-A continuous irradiation (30 mW/cm2). Follow-up examinations were scheduled on postoperative day 1; 1 and 2 weeks; 1, 3 and 6 months; and 1, 2 and 3 years. Main outcome measures were maximum corneal power (Kmax), average corneal power (AvgK), steepest corneal power (Ks), central corneal thickness, thinnest corneal thickness, uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BCVA) and endothelial cell density. RESULTS: Mean Kmax, AvgK, Ks, UCVA, BCVA and endothelial cell density did not significantly change over 3 years. The speed of progression obtained by linear regression analysis on corneal parameters (Kmax, AvgK, Ks) improved after ATE-CXL. All baseline parameters correlated with the postoperative Kmax slope. Two eyes underwent ATE-CXL redo because of continued progression after the primary CXL. CONCLUSION: This is the first report of 3-year results of ATE-CXL with 30 mW/cm2 × 3 min. ATE-CXL (30 mW/cm2 × 3 min) was safe and effective for slowing down KCN progression. TRIAL REGISTRATION NUMBER: This study was registered with ID UMIN000009372 in UMIN-Clinical Trials Registry.

Spontaneous Corneal Graft Reattachment Following Descemet Stripping Automated Endothelial Keratoplasty in Prone Position: A Case Report and Literature Review.

Graft detachment after Descemet stripping automated endothelial keratoplasty (DSAEK) is usually managed with air-bubbling. However, it is an invasive procedure, which can cause corneal endothelial reduction, and requires hospitalization and supine position maintenance. Only few case reports on graft reattachment in the prone position exist, and this is the first report from Japan. An 87-year-old woman presented with sudden pain in her left eye. Examination of her left eye showed a best-corrected vision of 20/50, shallow anterior chamber, cataractous lens, central corneal thickness (CCT) of 630 µm, and corneal endothelial cell count of 467 cells/mm2. She was diagnosed with left-eye bullous keratopathy due to primary angle closure, and DSAEK was performed after cataract surgery. Post-surgery, she touched her left eye due to agitation. Graft adhesion was good until postoperative day 4; however, a partial detachment was observed on day 12. She was instructed to remain in a prone position for as long as possible; on day 22, the graft was reattached, and the CCT improved to 555 µm. Since then, the graft adhesion has been maintained, and her best-corrected vision has improved to 20/30. To date, 5 cases of graft reattachment in the prone position have been reported, with reattachment observed in all cases within 10 days from the onset of detachment, including this case. Re-bubbling is an effective technique; however, it is invasive and may cause additional corneal endothelial loss. Therefore, it may be beneficial to have the patient initially attempt the prone position for reattachment.

Comparison of efficacy and safety of accelerated trans-epithelial crosslinking for keratoconus patients with corneas thicker and thinner than 380µm.

PURPOSE: Accelerated trans-epithelial cross-linking (ATE-CXL), a therapy to halt keratoconus progression, has the merit of widening the indications for thinner corneas (<380 µm). Since a hypotonic solution affects the swollen cornea, corneas of <380 µm thickness at preoperative measurement can be an indication for ATE-CXL. The aim of this retrospective study was to compare the efficacy and safety of ATE-CXL for keratoconus between corneas with thicknesses <380 µm and ≥380 µm. MATERIALS AND METHODS: Thirty-four eyes of 27 patients who underwent ATE-CXL (30 mW/cm2; 3 minutes) with completion of a 24-month follow-up, were enrolled and divided into two groups: Group 1, thinnest corneal thickness (TCT), <380 µm (n = 10) and Group 2, TCT, ≥380 µm (n = 24). A hypotonic solution was administered to Group 1 until the corneal thickness increased by >380 µm before UV-A irradiation. We measured uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), maximum and average keratometric values (Kmax and AveK), central corneal thickness (CCT), TCT by anterior segment optical coherence tomography, and corneal endothelial cell density (ECD) using specular microscopy. The changes from baseline to 24 months postoperatively between the two groups were compared accordingly. RESULTS: The changes in Kmax and AveK from baseline to 24 months in Group 1 (ΔKmax: -7.8 ± 7.7 D, ΔAveK: -4.3 ± 6.1 D) showed significant decreases compared to those in Group 2 (ΔKmax: 0.2 ± 3.0 D, ΔAveK: 0.6 ± 2.7 D) (p = .004 and p = .001), and there were no significant changes from baseline to 24 months postoperatively in UCVA, BCVA, CCT, TCT, and ECD in both groups. CONCLUSION: ATE-CXL is effective and safe for keratoconic corneas in both groups. The effect of reducing keratometric values was greater in the group with thinner corneas.

Corneal irregularity and visual function using anterior segment optical coherence tomography in TGFBI corneal dystrophy.

The purpose of this study was to evaluate corneal irregular astigmatism of patients with granular and lattice corneal dystrophy (GCD and LCD). 70 GCD, 35 LCD, and 81 control eyes were included. Anterior and posterior corneal topographic data obtained from anterior segment optical coherence tomography were expanded into four components via Fourier harmonic analysis. These components were compared with healthy eyes and the association between each component and best-corrected visual acuity (BCVA) was investigated. Anterior and posterior components increased in both GCD and LCD eyes. Anterior and posterior components of GCD2, anterior of LCD type 1 (LCD1), posterior of LCD type IIIA (LCD 3A), and type IV (LCD4) significantly increased. BCVA was significantly associated with anterior and posterior components in LCD eyes but not in GCD. The anterior components of LCD1, anterior and posterior of LCD3A, and posterior of LCD4 , were positively correlated with BCVA. As conclusions, in GCD eyes, anterior and posterior components differed from those of the control but BCVA was not significantly associated with them. In LCD eyes, the anterior and posterior components increased, and BCVA was significantly associated with the anterior and posterior components.

Corneal Graft Rejection after Descemet's Membrane Endothelial Keratoplasty with Peripheral Anterior Synechiae.

Descemet's membrane endothelial keratoplasty (DMEK) for patients with corneal endothelial loss rarely results in graft rejection. Herein, we report a rare case of graft rejection following DMEK, in which peripheral anterior synechiae were observed postoperatively. A 66-year-old woman was referred to our hospital after complaints of decreased visual acuity of her right eye after laser iridotomy for primary angle closure 3 years earlier. Her right cornea had bullous keratopathy with mild cataract, and her best-corrected visual acuity (BCVA) was 20/40. After cataract surgery, DMEK was successfully performed, except for development of peripheral anterior synechiae at the temporal cornea. Her BCVA recovered to 20/20. However, when topical instillation was changed to 0.1% fluorometholone from 0.1% betamethasone once a day, corneal edema reappeared with hyperemia, mutton fat keratic precipitates (KPs), and cells in the anterior chamber. The BCVA worsened to 20/32. Graft rejection was diagnosed, and subconjunctival injection of dexamethasone was performed 3 times, once every few days, with 0.1% topical betamethasone instillation. Subsequently, the hyperemia, mutton fat KPs, and cells in the anterior chamber disappeared with a recovered BCVA of 20/20 after 2 weeks. Ten months after graft rejection, there was no recurrence of intraocular inflammation, and only topical betamethasone was administered twice daily. It is important to exercise caution in cases with peripheral anterior synechiae after DMEK. Long-term steroid administration is necessary to prevent graft rejection.

Severe metabolic acidosis causes early lethality in NBC1 W516X knock-in mice as a model of human isolated proximal renal tubular acidosis.

We have identified a novel homozygous nonsense mutation (W516X) in the kidney-type electrogenic sodium bicarbonate cotransporter 1 (NBC1) in a patient with isolated proximal renal tubular acidosis (pRTA). To specifically address the pathogenesis of this mutation, we created NBC1 W516X knock-in mice to match the patient's abnormalities. The expression of NBC1 mRNA and protein in the kidneys of NBC1(W516X/W516X) mice were virtually absent, indicating that nonsense-mediated mRNA decay (NMD) is involved in the defective transcription and translation of this mutation. These mice not only recapitulated the phenotypes of this patient with growth retardation, pRTA, and ocular abnormalities, but also showed anemia, volume depletion, prerenal azotemia, and several organ abnormalities, culminating in dehydration and renal failure with early lethality before weaning. In isolated renal proximal tubules, both NBC1 activity and the rate of bicarbonate absorption were markedly reduced. Unexpectedly, there was no compensatory increase in mRNA of distal acid/base transporters. Sodium bicarbonate but not saline administration to these mutant mice markedly prolonged their survival, decreased their protein catabolism and attenuated organ abnormalities. The prolonged survival time uncovered the development of corneal opacities due to corneal edema. Thus, NBC1(W516X/W516X) mice with pRTA represent an animal model for metabolic acidosis and may be useful for testing therapeutic inhibition of NMD in vivo.

Specific tear IgE in patients with moderate-to-severe autumnal allergic conjunctivitis.

BACKGROUND: Recently, a new commercial test for specific IgE based on immunochromatography (Immfast Check J1®) has been developed. We previously reported on the use of this kit for tear fluid samples during spring. In this study, we compared the level of specific IgE in tear fluid among patients with seasonal allergic conjunctivitis during spring or autumn and control subjects. METHODS: A nonrandomized, cross-sectional study was conducted in patients with moderate-to-severe allergic conjunctivitis occurring in spring (n = 56, spring group) or autumn (n = 52, autumn group), as well as in age- and sex-matched healthy control subjects (n = 50, control group). Levels of specific IgE for cedar pollen, cat epithelium and Dermatophagoides pteronyssinus were measured in tear fluid with the Immfast Check J1. RESULTS: Specific IgE scores for cedar pollen and D. pteronyssinus were significantly higher in the spring and autumn groups than in the control group (p < 0.0001). In the autumn group, the highest detection rate for a specific allergen was 96.2% for D. pteronyssinus, followed by cedar pollen (86.5%) and cat epithelium (25.5%). In the spring group, the highest detection rate was 98.3% for cedar pollen, followed by D. pteronyssinus (51.7%) and cat epithelium (19.0%). CONCLUSIONS: These results suggest that both house dust mite allergen and outdoor allergens such as cedar pollen can be causes of allergic conjunctivitis during both spring and autumn in Japan. The Immfast Check J1 provides rapid measurement of specific IgE in tear fluid, which allows easy diagnosis of allergic conjunctivitis in an outpatient setting.

Relationship between total tear and serum IgE in allergic conjunctivitis.

BACKGROUND: Recently, a new commercial test for total tear IgE based on immunochromatography (Allerwatch®) was developed. We examined the relationship between total tear and serum IgE levels with the Allerwatch test. METHODS: A nonrandomized cross-sectional study was conducted in 40 patients with allergic conjunctivitis, 35 age- and sex-matched healthy control subjects, and 6 patients with epidemic keratoconjunctivitis (EKC). The total tear IgE score was determined with the Allerwatch test (0, 1 and 2), and the serum total IgE level was measured by solid-phase immunoassay (Phadezym PRIST) in all subjects. RESULTS: Total tear IgE was assayed within 10 min of collection in all samples. The total tear IgE-positive rate was significantly higher in the allergic group than in the control and EKC groups (92.5 vs. 0.0 vs. 0.0%; p < 0.00001). Sensitivity and specificity were 0.925 and 1.000, respectively. The total IgE score and log (total serum IgE) were also higher in the allergic group than in the control and EKC groups [total IgE score: 1.48 ± 0.63 vs. 0.00 ± 0.00 vs. 0.00 ± 0.00, p < 0.00001; log (serum total IgE): 2.23 ± 0.50 vs. 0.80 ± 0.31 vs. 0.79 ± 0.37, p < 0.00001]. The total tear IgE score was significantly correlated with log (total serum IgE) in the allergic group (r = 0.712, p < 0.00001). CONCLUSIONS: These results show that this rapid test for the measurement of total tear IgE is easy to perform on an outpatient basis and may be helpful in the management of ocular allergy.

Leukocytes mediate retinal vascular remodeling during development and vaso-obliteration in disease.

Retinal ischemia can cause vision-threatening pathological neovascularization. The mechanisms of retinal ischemia are not fully understood, however. Here we have shown that leukocytes prune the retinal vasculature during normal development and obliterate it in disease. Beginning at postnatal day 5 (P5) in the normal rat, vascular pruning began centrally and extended peripherally, leaving behind a less dense, smaller-caliber vasculature. The pruning was correlated with retinal vascular expression of intercellular adhesion molecule-1 (ICAM-1) and coincided with an outward-moving wave of adherent leukocytes composed in part of cytotoxic T lymphocytes. The leukocytes adhered to the vasculature through CD18 and remodeled it through Fas ligand (FasL)-mediated endothelial cell apoptosis. In a model of oxygen-induced ischemic retinopathy, this process was exaggerated. Leukocytes used CD18 and FasL to obliterate the retinal vasculature, leaving behind large areas of ischemic retina. In vitro, T lymphocytes isolated from oxygen-exposed neonates induced a FasL-mediated apoptosis of hyperoxygenated endothelial cells. Targeting these pathways may prove useful in the treatment of retinal ischemia, a leading cause of vision loss and blindness.

Relationship between conjunctivochalasis and refractive error.

OBJECTIVES: To assess the relation between the prevalence and grade of conjunctivochalasis and refractive error and to compare the grade of conjunctivochalasis between myopic and hyperopic patients. METHODS: Consecutive patients aged from 3 to 94 years were chosen for this study. Exclusion criteria included a history of using contact lenses, ocular surgeries, infectious conjunctivitis, or corneal diseases. The age, gender, medical history, ocular history, the grade and other parameters of inferior conjunctivochalasis classified into three locations (nasal, middle, and temporal), and refractive error were determined in all subjects. Patients were divided into three groups as follows: a hyperopic group (≥0.0 D), an emmetropic group (<0.0 and ≥-2.0 D), and a myopic group (<-2.0 D). They were also divided into 10 groups according to age. One-way analysis of variance and the Scheffe multiple comparison test were used to compare the mean values among three groups. Relations among the variables were investigated by calculating Pearson correlation coefficients and partial correlation coefficients. RESULTS: A total of 1,110 patients were included in the study. In each age group, the mean grade of conjunctivochalasis was higher in hyperopic patients than in myopic patients. There were no significant differences in both the downward gaze- and digital pressure-dependent changes of conjunctivochalasis between the myopic and hyperopic groups. The severity of conjunctivochalasis affecting the nasal and temporal bulbar conjunctiva, and parameters such as the changes of conjunctivochalasis caused by downward gaze or digital pressure, were correlated with the refractive error, especially in patients over 40 years old (P<0.05). CONCLUSIONS: This was the first assessment of the relationship between refractive error and the grade of conjunctivochalasis in a large consecutive series of patients. Our results suggest that the prevalence and grade of conjunctivochalasis are dependent on refractive error, with hyperopia being an important risk factor for conjunctivochalasis.

Severity and determinants of pinguecula in a hospital-based population.

OBJECTIVES: Pinguecula is a relatively frequent disease; however, there have been no reports about the grade of pinguecula. We investigated the relationship between age and the prevalence and severity of pinguecula by using a grading system and compared the grade of pinguecula between men and women and between the nasal and temporal halves of the conjunctiva. METHODS: This was a prospective, randomized study of 1,040 patients aged 1 to 95 years, including 520 men and 520 age-matched women. The age, gender, medical history, ocular history, and grade of pingueculae located on the nasal and temporal conjunctiva were determined in all subjects. RESULTS: The prevalence of pinguecula increased dramatically with age. The mean grade was higher in male patients than in female patients for pingueculae located on both the nasal conjunctiva (P = 0.00072) and the temporal conjunctiva (P = 0.00035). However, there was no significant difference in the grade of pinguecula between the nasal and temporal conjunctiva. CONCLUSIONS: This was the first assessment of the grade of pinguecula in a large series of patients. Our findings strongly suggest that pinguecula is an age-dependent lesion that occurs from young adulthood onward. The present grading system should also be useful for future clinical studies of pinguecula.

Laser treatment of giant iris cyst with nanophthalmos.

We report a case of a giant iris cyst treated with neodymium-doped yttrium aluminum garnet laser cystotomy. A 33-year-old woman presented with nanophthalmos and ocular hypertension secondary to a giant iris cyst after congenital cataract surgery in the left eye. Examination with a rotating Scheimpflug camera and anterior-segment optical coherence tomography revealed a large iris cyst surrounding the pupillary region. She underwent laser iridocystotomy and irrigation of the anterior chamber. No recurrence of the iris cyst has been noted after 18 months and the IOP is normal. The cyst was treated successfully by laser cystotomy without other ocular tissue damage. Examination with a rotating Scheimpflug camera and anterior-segment optical coherence tomography proved to be simple and quick methods for assessing the iris cyst.

Characteristics of astigmatism before and 1 month after blepharoptosis surgery in patients with acquired ptosis.

In this study, we aimed to evaluate the characteristics of astigmatism preoperatively and 1 month postoperatively in patients with age-related ptosis (AP) and contact lens-related ptosis (CLP), and investigate surgery-induced astigmatism (SIA) using the Jaffe vector analysis and the Cravy method. Consecutive patients who underwent blepharoptosis surgery between January 2019 and December 2019 were included. The patients were divided into AP and CLP groups. Computerized corneal topography was used to assess the magnitude and axis of corneal astigmatism. Astigmatism was classified as with-the-rule (WTR), against-the-rule (ATR), or oblique astigmatism (OA) pre- and postoperatively. SIA was calculated by vector analysis using the Cravy and Jaffe methods. The correlation between SIA and margin reflex distance (MRD) was calculated. One hundred and eight eyes from 58 patients (AP group: 85 eyes from 45 patients, CLP group: 23 eyes from 13 patients) were included. The AP group (73.8±7.6 years) was significantly older than the CLP group (47.7±6.6 years). The MRD increased significantly after treatment in both groups. The proportions of WTR, ATR, and OA were 52%, 22%, and 25%, and 86%, 9%, and 4% in the AP and CLP groups, respectively. A shift in astigmatism type was observed in 41% and 13% of patients in the AP and CLP groups, respectively. The average SIA measured using the Cravy method was 0.11±1.22 D in the AP group and -0.28±1.07 D in the CLP group (WTR astigmatism). The SIA calculated using the Jaffe method was 0.78±0.70 D in the AP group and 0.82±0.88 D in the CLP group. There was no significant correlation between SIA calculated using the Cravy and Jaffe methods and MRD. ATR was most common in age-related ptosis and WTR was most common in contact lens-related ptosis. Upper eyelid re-positioning may affect visual functions due to astigmatic changes in the short term postoperatively.