Young-Sik Yoo

Poly(ADP-Ribose) Polymerase Inhibition Improves Corneal Epithelial Innervation and Wound Healing in Diabetic Rats

PURPOSE We evaluated the effect of poly(ADP-ribose) polymerase (PARP) inhibition by using 1,5-isoquinolinediol (ISO) on corneal epithelial innervation in diabetic rats. METHODS ISO (3 mg/kg, intraperitoneal) or vehicle was administered to rats with diabetes induced by streptozotocin for 4 weeks. Epithelial innervation, epithelial wound healing, and corneal sensation were evaluated in diabetic rats (DM rats), diabetic rats treated with ISO (DM-ISO rats), and nondiabetic (non-DM) rats. The density of epithelial innervation was calculated separately as nerve terminals and sub-basal nerve plexus by analyzing the images of whole-mount corneas. Healed areas of epithelial defect were measured at 0, 18, and 36 hours after creating a 4-mm wound on the cornea. Corneal sensitivity test was conducted using a Cochet-Bonnet handheld esthesiometer. Additionally, PARP1 and poly(ADP-ribosyl)ated polymers (pADPr) as its products, were identified in trigeminal ganglions (TGs) by Western blot analysis and immunofluorescence staining. RESULTS In DM rats, the density of nerve terminals (5.57% ± 0.94%) and sub-basal nerve plexus (22.08 ± 1.78 mm/mm(2)) was significantly reduced in comparison with that in DM-ISO rats (8.64% ± 1.42%, 30.82 ± 2.01 mm/mm(2), respectively) and non-DM rats (9.02 ± 1.14%, 34.77 ± 4.45 mm/mm(2), respectively). The percentages of healed area of the epithelial defects at 18 and 36 hours were significantly smaller in DM rats (23.8 ± 5.2%, 53.2 ± 4.6%, respectively) than in DM-ISO rats (43.2 ± 1.4%, 75.8 ± 2.2%, respectively) and non-DM rats (48.1 ± 8.6%, 86.1 ± 3.3%, respectively). Corneal sensitivity decreased in DM rats (51.1 ± 0.3 mm) but not in DM-ISO rats (57.8 ± 0.2 mm). There were no differences between parameters in DM-ISO rats and those in non-DM rats. CONCLUSIONS Diabetic corneas showed loss of epithelial innervation, resulting in delayed epithelial healing and decreased corneal sensitivity. Inhibition of poly(ADP-ribose) polymerase (PARP) with 1,5-isoquinolinediol alleviated these diabetes-induced alterations in the corneal epithelium in the diabetic rats.

Tear Osmolarity and Ocular Surface Parameters as Diagnostic Markers of Ocular Graft-Versus-Host Disease.

PURPOSE To evaluate the diagnostic value of tear osmolarity and several ocular surface parameters in screening for ocular surface alterations in ocular graft-vs-host disease (GVHD) patients. DESIGN Case-control study. METHODS Sixty-three patients with ocular GVHD and 74 healthy participants were screened for ocular surface changes using the Ocular Surface Disease Index (OSDI), tear osmolarity, Schirmer test, tear break-up time (TBUT), and fluorescein corneal staining. The severity of ocular GVHD was diagnosed according to the National Institutes of Health (NIH) grading system. The diagnostic sensitivity and specificity and cutoff values were determined for each ocular parameter using a receiver operating characteristic (ROC) curve and area under the curve (AUC) analysis. Significance was defined at P < .05. RESULTS The tear osmolarity, corneal staining score, and OSDI score gradually increased as the severity of ocular GVHD increased, and Schirmer value gradually decreased as the GVHD grade increased in severity. The Schirmer test showed greatest diagnostic sensitivity and specificity for ocular GVHD (92.1% sensitivity, 85.7% specificity, cutoff = 9 mm), followed by the TBUT (87.3% sensitivity, 75.0% specificity, cutoff = 6 s), tear osmolarity (98.4% sensitivity, 60.7% specificity, cutoff = 311 mOsm/L), corneal staining score (66.7% sensitivity, 82.1% specificity, cutoff = 2), and OSDI score (77.8% sensitivity, 66.1% specificity, cutoff = 20.8). CONCLUSIONS Multiple diagnostic modalities should be used to detect ocular surface changes in GVHD patients. The severity of ocular GVHD can be effectively monitored using tear osmolarity; however, additional studies are required.

Examination of Gland Dropout Detected on Infrared Meibography by Using Optical Coherence Tomography Meibography

PURPOSE To elucidate the anatomic details of gland dropout detected on two-dimensional infrared (IR) meibography in cases of dry eye associated with meibomian gland dysfunction (MGD) by using three-dimensional optical coherence tomography (OCT) meibography. METHODS In this cross-sectional, observational case series, we enrolled gland dropout detected on IR meibography; the condition was then examined using a real-time swept-source OCT system. Accordingly, a series of 500 raster B-scan OCT images, with the gland dropout site (observed on IR imaging) at the center, were obtained and rendered as three-dimensional volume images. The OCT images were classified based on the anatomic details, including acini and ducts, at the meibomian glands (Group I, constricted acini; II, atrophic acini; III, no acini). RESULTS The percentage of disagreement between IR and OCT images for dropout detected on IR imaging was 49.45% (43 and 93 cases in group I and II, respectively). Loss of the meibomian glands on both IR and OCT imaging (Group III) was observed in 50.55% cases (133 and 6 cases of gland dropout at the partial and whole eyelid on IR imaging, respectively). The proportion of disagreement between IR and OCT images (Group I and II) was higher in the middle area (63/119, 53.39%), as compared to that in the nasal (34/73, 46.58%) or temporal areas of the eyelid (26/65, 40%). CONCLUSIONS The loss of the meibomian glands, as observed on IR imaging, should be carefully interpreted, and OCT images may be useful to confirm the anatomic details of the meibomian glands.

The Influence of Overnight Orthokeratology on Ocular Surface and Meibomian Glands in Children and Adolescents.

Purpose: The aim of this study was to investigate the influence of overnight orthokeratology (OOK) on ocular surface and meibomian glands in children and adolescents. Methods: Prospective, noncomparative study included the ocular surface disease index (OSDI), tear osmolarity, corneal and conjunctival fluorescein staining, tear film breakup time (TBUT), the Schirmer I test, and meiboscore using noncontact meibography. Immunofluorescence confocal microscopy of interleukin-1&bgr; (IL1&bgr;), interleukin-6 (IL6), epidermal growth factor (EGF), and matrix metalloproteinase (MMP)-9 using impression cytology filter paper was performed. The tests were performed before and at 6, 12, 24, and 36 months after OOK wear. Results: Fifty-eight subjects using OOK were observed. Significant increases in OSDI score (P=0.0009) and corneal and conjunctival staining score (P<0.0001) were observed compared with baseline values at 36 and 24 months, respectively. Ocular surface and meibomian changes were noted in 2 patients (3.5%). One patient exhibited an increase in OSDI score, concurrent with a decrease in TBUT at 36 months and minor loss of the meibomian gland at the distal portion of the lower lid at 24 months. The other patients exhibited the development of papillary hypertrophy and meibomian gland distortion at 24 months. No significant changes were detected in IL1&bgr;, IL6, EGF, or MMP expression after OOK use. Conclusion: Based on the findings, OOK was a relatively safe modality. However, given the potential changes in the meibomian gland and tear film stability, special attention must be paid to children with baseline meibomian gland distortions or a history of allergic conditions.

Evaluation of optical performance of 4 aspheric toric intraocular lenses using an optical bench system: Influence of pupil size, decentration, and rotation.

Purpose To evaluate the effect of pupil size, degree of intraocular lens (IOL) decentration, and rotation of 4 aspheric toric IOLs on the image quality. Setting Department of Ophthalmology, Seoul St. Mary’s Hospital, Seoul, South Korea. Design Experimental study. Methods Four aspheric toric intraocular lenses (IOLs)—the Precizon (transitional conic toric IOL), AT Torbi 709M (bitoric IOL), SN6AT4 (posterior toric surface IOL), and ZCT225 (anterior toric surface IOL)—were evaluated using the optical bench metrology system. Measurements included changes in spherical aberrations, relative spherical equivalent (SE), and image quality at different pupil diameters and image quality degradation due to decentration and rotation of the IOLs. Results Change in relative SE with pupil size in aberration‐free toric IOLs (transitional conic toric and bitoric IOLs) was greater than in negatively aspheric toric IOLs (posterior toric surface and anterior toric surface IOLs). In contrast, the aberration‐free IOLs showed higher contrast than the negatively aspheric IOLs. When IOLs were decentered by 1.0 mm, the contrast reduction rates at 17.6 cycles per degree for the transitional conic toric IOL, bitoric IOL, posterior toric surface IOL, and anterior toric surface IOL were 5.1%, 3.1%, 12.2%, and 15.8%, respectively. Rotation‐induced deterioration of contrast to 0.5 required a much higher rotation for the transitional conic toric IOL than for the other 3 IOLs. Conclusions The transitional conic toric IOL and bitoric IOL provided superior image quality despite pupil size changes and the presence of decentration. The transitional conic toric IOL demonstrated maximum rotation tolerance compared with the other IOLs. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

POSTERIOR EYE SEGMENT COMPLICATIONS RELATED TO ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION.

Purpose: To identify complications in the posterior eye segment in patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT). Methods: This retrospective cohort study enrolled 747 patients with hematologic disease who had undergone allogeneic HSCT at Seoul St. Marys Hospital from January 2009 to December 2012. The posterior eye segment complications were evaluated by reviewing information in medical records at the Department of Hematology and Ophthalmology, including the types, onset times, locations, and resolution times of the complications according to the treatment periods for HSCT; in addition, a subgroup analysis was performed. Results: Among the 635 included patients, 48 (7.6%) experienced complications related to HSCT in the posterior eye segment. Twenty patients were diagnosed with retinal hemorrhage, 16 with cytomegalovirus (CMV) retinitis, and 5 with uveitis. Six patients (37.5%) with retinal hemorrhage had a lesion in Zone 1 and took more time to recover from this complication. Retinal tear (1/16, 6.3%) and rhegmatogenous retinal detachment (2/16, 12.5%) were observed in the patients with CMV retinitis. Among the 20 patients with retinal hemorrhage, 18 (90.0%) had thrombocytopenia, 14 (70.0%) had pancytopenia, and 7 (35.0%) had profound cytopenia. Cytomegalovirus viremia was detected in 16 (72.7%) of the 22 patients with inflammation-associated complications. Conclusion: Understanding of each patients general condition, which is affected by the specific procedures used for HSCT, is important for the diagnosis and management of transplantation-related complications in the posterior eye segment.

Changes of meibomian glands in the early stage of post hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) is the most effective cure for hematologic malignancies. Graft-versus-host disease (GVHD) is a major complication following allogeneic HSCT, which significantly affects non-relapse mortality. And ocular manifestations of GVHD are known to occurin 60-90% of patients with chronic GVHD. Although the pathogenesis of ocular GVHD is not clearly known, it is known to progress into inflammation and fibrosis through presentation of antigens on CD4 and CD8 T cells. There is much evidence that the ocular surface and meibomian glands are severely damaged in ocular GVHD patients, and there are few observational studies on the early changes. In this review, we will discuss the various changes in the meibomian glands and ocular surface, and tear dynamics in the early stage following HSCT. These results show that tear film break-up time (TFBUT) decreased and the corneal staining score was significantly higher 2-3 months after HSCT. The upper eyelid and total eyelid meiboscore increased after 3 months following HSCT. The information of the early changes of meibomian glands morphology would be helpful to further examine the pathogenesis of meibomian gland dysfunction.

Through-focus optical characteristics of monofocal and bifocal soft contact lenses across the peripheral visual field

To characterise the impact of monofocal soft contact lens (SCL) and bifocal SCLs on refractive error, depth of focus (DoF) and orientation of blur in the peripheral visual field.

Morphological evaluation for diagnosis of dry eye related to meibomian gland dysfunction

The evaluation of morphological changes of the acini in the meibomian glands is important for the diagnosis and management of dry eye related to meibomian gland dysfunction. While several tools have been developed to detect meibomian gland structure, infrared imaging is generally used in clinical settings. Unlike the lipid component analysis of tear film in which quantitative analysis is possible, the meibomian glands are limited to qualitative analysis because of the low image quality of the diagnostic tools. This review describes diagnostic tools, especially in terms of morphological evaluation of the acini, which are visualized by the existence of lipid within them.

Difference in Outcomes between First-Operated vs. Fellow-Operated Eyes in Patients Undergoing Bilateral Trabeculectomies.

Main Objective To compare the course and outcome of first- and fellow-operated eyes in patients who underwent bilateral trabeculectomies and to investigate the factors associated with the difference. Methods Preoperative characteristics, including the interval between surgeries, were compared between the first- and fellow-operated eyes in 42 patients who underwent bilateral trabeculectomies. Postoperative intraocular pressure and bleb vascularity, using postoperative anterior segment photos, were compared at various time points between the first- and fellow-operated eyes. Surgical success was evaluated at 1 year after surgery and at the final follow-up. Factors affecting the difference between the first and fellow eyes were analyzed. Results There was no significant difference in success or failure rates at 1 year postoperatively and at the final follow-up between the first- and fellow-operated eyes. Early postoperative IOP and the degree of bleb vascularity were higher in the fellow-operated eyes (P = 0.001 and 0.003, respectively at week 1 postoperative). The difference in IOP between the first- and fellow-operated eyes was greater in patients whose interval between surgeries was shorter than 3 weeks (P = 0.026). Conclusions In patients undergoing bilateral trabeculectomies, early postoperative IOP was higher in the fellow-operated eyes than the first-operated eyes; the difference was greater when the interval between surgeries was shorter. The first-operated eye may influence the early postoperative inflammatory response in the fellow-operated eye. Our findings have clinical implications for planning treatment of patients who may need bilateral surgery.