Outcomes of surgical bleb revision at a tertiary Singapore eye hospital.

PURPOSE: To describe the outcomes of surgical bleb revisions from a tertiary glaucoma service in Singapore. METHODS: One hundred and thirty-one eyes of 129 patients who underwent surgical bleb revisions at the Singapore National Eye Centre between 2007 and 2014 were included in the study. The indications for bleb revision were: bleb-related infection (BRI), early and late bleb leak, early and late overfiltration, and bleb dysesthesia. Regression analysis was applied to elucidate risk factors. RESULTS: The mean age of the patients was 66 years, 62.6% were male, and 88.5% were Chinese. The majority of the eyes had primary glaucoma (79.4%). The mean interval from the initial trabeculectomy or phaco-trabeculectomy to the bleb revision was 58.8 months. The overall success rate was 69.5%. By Kaplan-Meier survival analysis, the overall cumulative success range fell from 78.6% to 49.1% over 10 years. Eyes with early bleb leak had lower surgical success compared to eyes with late bleb leak, early overfiltration and late overfiltration (P = 0.026, log-rank test). The IOP improved significantly post-operatively for eyes with BRI, early bleb leak, late bleb leak, early overfiltration and overfiltration (P < 0.05). Vision improved significantly in eyes with early overfiltration, but deteriorated in eyes with BRI (P < 0.05). CONCLUSION: The overall success rate for surgical bleb revisions was good with complete resolution of the primary problem in the majority of cases. However, eyes with early bleb leak were less likely to have successful outcomes and should be monitored more closely post-operatively.

Outcomes of combined single-use dual blade goniotomy and cataract surgery.

PURPOSE: Single-use dual blade goniotomy (SBG) is a novel ab interno procedure that removes three to five clock hours of trabecular meshwork (TM). We analysed the reduction of intraocular pressure (IOP) and topical glaucoma medication (Meds) in eyes following combined cataract surgery and SBG (Cat-SBG). METHODS: IOP and Meds were evaluated retrospectively in 55 eyes of 38 patients. 44 eyes had high tension glaucoma (HTG) and eleven eyes had normal tension glaucoma (NTG). Complete success (no Meds) and qualified success (with Meds) for IOP levels ≤ 21, ≤ 18 , ≤ 16 mmHg or ≥ 20% IOP reduction at the two- and six-month follow-up were evaluated. RESULTS: IOP and Meds were significantly reduced from before to two months after Cat-SBG in HTG- and NTG-patients (HTG: IOP 19.4 ± 3.3 to 15.1 ± 3.3 mmHg; p < 0.001; Meds 2.1 ± 1.3 to 0.8 ± 1.3; p < 0.001; NTG: IOP 14.0 ± 2.3 to 11.5 ± 2.3 mmHg; p = 0.004; Meds 1.6 ± 0.7 to 0.3 ± 0.7; p < 0.001). IOP and Meds did not change significantly from two to six months after Cat-SBG. In HTG, complete and qualified success rates were 43% (19/44) and 93% (41/44) for IOP ≤ 18 mmHg, 36% (16/44) and 64% (28/44) for IOP ≤ 16 mmHg and 30% (13/44) and 43% (19/44) for ≥ 20% IOP reduction six months after surgery. In NTG, complete and qualified success was 81% (9/11) and 100% (11/11) for IOP ≤ 18 and ≤ 16 mmHg, and 27% (3/11) for IOP reduction ≥ 20%. IOP and Meds reduction were comparable between HTG and NTG eyes. Only minor postoperative complications occurred. CONCLUSION: Cat-SBG is an efficient method to significantly lower IOP in patients with HTG and NTG.

Femtosecond laser-assisted stromal keratophakia for keratoconus: A systemic review and meta-analysis.

PURPOSE: Femtosecond lasers have revived the possibility of stromal keratophakia or tissue additive keratoplasty, a technique originally introduced by Prof. Jose Ignacio Barraquer in the 1960s. The surgical technique offers a unique solution to treat keratoconus. In the current study, we reviewed and performed a meta-analysis of the clinical outcomes of the femtosecond laser-assisted stromal keratophakia in the treatment of keratoconus. METHODS: This is a systematic review and meta-analysis of the estimated outcome difference between pre- and post-lenticule implantations. RESULTS: A total of related 10 studies were found in the literature. No studies reported adverse events, such as persistent haze or graft rejection, at last patients' visits. We further narrowed down the article selection in accordance to our inclusion criteria to report the composite outcomes (9 studies) and meta-analysis (4 studies). In the composite analysis, we demonstrated that lenticule implantation in keratoconus and post-LASIK ectasia patients appeared to expand the stromal volume of the thin corneas, flattened the cones, and significantly improved uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA) and spherical equivalent (SE). The meta-analysis showed that the random estimated UCVA, BCVA, SE and mean keratometry (Km) differences following the lenticule implantation was -0.214 (95% CI: -0.367 to 0.060; p = 0.006), -0.169 (-0.246 to 0.091; p < 0.001), -2.294 D (-3.750 to -0.839 D; p = 0.002), and 2.909 D (0.805 to 5.012 D; p = 0.007), respectively. CONCLUSIONS: Femtosecond laser-assisted stromal keratophakia is a feasible technique to correct the refractive aberrations, expand corneal volume and regularize corneal curvature in patients with keratoconus. However, there is a need to standardize the technique (e.g., whether to crosslink or not or to use convex or concave lenticules) and to formulate a mathematical model that accounts for the long-term epithelial thickness changes and stromal remodeling to determine the shape or profile of the lenticules, in order to improve the efficacy of the keratophakia further.

Comparison of Corneal Epithelial and Stromal Thickness between Keratoconic and Normal Eyes in an Asian Population.

PURPOSE: To assess corneal epithelial and stromal thickness in keratoconic and normal eyes by spectral domain optical coherence tomography (SDOCT) in an Asian population. METHODS: Forty-three keratoconic and 24 normal eyes were studied and examined using SDOCT. Keratoconic eyes with corneal scarring were excluded. Epithelial and stromal thickness was assessed at 25 points, 0.5 mm apart, across the central 6 mm of the pupil centre in the horizontal and vertical meridians. The correlation between epithelial and stromal thickness in both keratoconic and normal eyes (at the corneal centre) was also assessed. RESULTS: The corneal epithelium at the pupil centre was significantly thinner in keratoconic eyes (p < 0.05) than in controls. Epithelial thickness varied widely in keratoconic eyes compared to controls (p < 0.05). The epithelium and stroma were significantly thinner inferiorly and temporally in keratoconic eyes (p < 0.05). There was a significant correlation between epithelial and stromal thickness (at the pupil centre) in the keratoconus group (rs = 0.348, p < 0.001) but not the normal group (rs = 0.036, p = 0.376). CONCLUSIONS: Corneal epithelial thickness was markedly thinner and varied in keratoconic eyes compared to controls. Epithelial thinning occurred secondary to the abnormal elevation of the stroma. These findings are useful in detecting early keratoconus and in the evaluation of refractive surgery candidates.

Long-term follow-up of deep anterior lamellar keratoplasty after Descemet stripping automated endothelial keratoplasty.

AIMS: To describe the long-term outcomes of deep anterior lamellar keratoplasty (DALK) performed after Descemet stripping automated endothelial keratoplasty (DSAEK) in cases of infection and residual stromal opacity. METHODS: Ten eyes of nine consecutive patients undergoing DALK after DSAEK at a single tertiary referral center (SNEC) from 2011 to 2016 were analyzed for best spectacle-corrected visual acuity (BSCVA), refraction, spherical equivalent (SE) and cylinder, as well as graft diameters, survival, and complications. RESULTS: The mean pre-DSAEK BSCVA was 1.73 ± 0.76 LogMAR. At a mean follow-up of 9.8 ± 7.1 months, visual acuity had improved significantly (p = 0.028) to 1.09 ± 0.55 LogMAR after DSAEK. DALK was performed at 10.3 ± 7.2 months after DSAEK because of residual stromal scarring in nine and a corneal infection in one case. At the last follow-up visit (19.4 ± 13.9 months) after DALK, BSCVA had improved to 0.38 ± 0.6 LogMAR, significantly better than after DSAEK alone (p = 0.015) and before DSAEK (p = 0.018). Spherical equivalent (- 4.8 ± 3.5 D) and cylinder (- 2.5 ± 2.0 D) did not show significant changes compared to after DSAEK (SE p = 0.17; cylinder p = 0.19) or 3 months after DALK (SE p = 0.17; cylinder p = 0.46). One endothelial graft failed 3 months after DALK. Kaplan-Meier estimated average survival for all cases was 45.3 (95% CI 36.6-54.0) months. The cumulative survival probability for the entire cohort was 90% at 1, 2, and 4 years of follow-up. CONCLUSIONS: DALK surgery after DSAEK can improve vision in cases of residual host scarring and treat host corneal infection, while avoiding open-sky surgery and sparing a healthy endothelial graft.

XEN-45 collagen implant for the treatment of uveitic glaucoma.

IMPORTANCE: The XEN-45 implant, a hydrophilic collagen implant which drains aqueous to the subconjunctival space, has not been investigated in the context of uveitic glaucoma. BACKGROUND: To determine the safety and efficacy of the XEN-45 collagen implant in eyes with uveitic glaucoma. DESIGN: Exploratory prospective case series. PARTICIPANTS: patients with medically uncontrolled uveitic glaucoma. METHODS: Twenty-four consecutive patients (mean age ± standard deviation [SD] = 45.3 ± 18.1 years) were implanted with the XEN-45 implant. MAIN OUTCOME MEASURES: The primary outcome measure was intraocular pressure (IOP) reduction at 12 months as compared to baseline. Secondary outcome measures included ocular hypotensive medication use at 12 months, the requirement for further glaucoma surgery and failure. Intraoperative and postoperative complications were documented. RESULTS: The baseline mean ± SD IOP was 30.5 ± 9.8 mmHg and the mean ± SD number of glaucoma medications required was 3.3 ± 0.8. In 20 eyes (83.3%) in whom conventional glaucoma surgery was originally perceived to be inevitable, further surgery was not required after XEN-45 implantation. The mean IOP was reduced by 60.2% from baseline to 12.2 ± 3.1 mmHg and mean medication usage was reduced to 0.4 ± 0.9 at 12 months (both P < 0.001). One patient had hypotony persisting beyond 2 months that required surgical revision and one patient developed blebitis. The 12-month cumulative Kaplan-Meier survival probability was 79.2%. CONCLUSIONS AND RELEVANCE: The XEN-45 implant is effective for the treatment of patients with medically uncontrolled uveitic glaucoma. Potentially sight-threatening complications, including bleb-related ocular infection and persistent hypotony, may occur.

Five-Year Graft Survival Comparing Descemet Stripping Automated Endothelial Keratoplasty and Penetrating Keratoplasty.

PURPOSE: To compare 5-year graft survival after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) in Asian eyes. DESIGN: Prospective, nested, cohort study. PARTICIPANTS: Consecutive patients who underwent DSAEK (423 eyes) or PK (405 eyes) for Fuchs' endothelial dystrophy (FED) or bullous keratopathy (BK). METHODS: Clinical data and donor and recipient characteristics were recorded from our prospective cohort from the Singapore Corneal Transplant Registry. All surgeries were performed by the corneal surgeons at our center, which included cases performed or partially performed by corneal fellows in training under direct supervision. MAIN OUTCOME MEASURES: Five-year cumulative graft survival. RESULTS: Overall mean age was 67.8±9.8 years, and 50.1% of patients were men. There were no significant differences in age (P = 0.261) or gender (P = 0.78) between PK and DSAEK groups in our predominantly Chinese (76.6%) Asian cohort, with more BK compared with FED (68.1% vs. 31.9%; P < 0.001). Overall 5-year graft survival was superior for DSAEK compared with PK (79.4% vs. 66.5%; P < 0.001, log-rank test). Median 5-year percent endothelial cell density loss was significantly greater in PK compared with DSAEK (60.9% vs. 48.7%; P = 0.007). Cox regression analysis revealed that BK was a significant factor associated with graft failure (hazard ratio [HR], 3.30; 95% confidence interval [CI], 2.05-5.33; P < 0.001), and PK was more likely to fail compared with endothelial keratoplasty (HR, 1.61; 95% CI, 1.08-2.41; P = 0.02) adjusting for confounders such as recipient age, gender, and donor factors. Five-year cumulative incidence of complications such as graft rejection (P < 0.001), epitheliopathy (P < 0.001), suture-related corneal infections (P < 0.001), and wound dehiscence (P = 0.002) were greater in the PK group compared with the DSAEK group. CONCLUSIONS: In Asian eyes from the same study cohort with standardized surgical and postoperative regimes, 5-year graft survival was superior for DSAEK compared with PK in eyes with FED and BK.

Effect of anti-VEGF on retinal blood flow in diabetic mice using laser speckle flowgraphy.

PURPOSE: To assess intra- (repeatability) and inter-observer (reproducibility) variability of laser speckle flowgraphy (LSFG) for retinal blood flow (RBF) measurement in 20 eyes of wild type (C57BL/6J) mice and effect of intravitreal Aflibercept on RBF in optic nerve head (ONH) region of 10 eyes of Ins2 (Akita) diabetic mice. METHODS: 'Mean blur rate (MBR)' was measured for all quadrants of tissue area (MT), vessel (MV) and total area (MA) of ONH region. Changes in MT were analysed at each timepoint. Repeatability was evaluated by measuring MBR variability without changing mouse head position, and reproducibility after resetting mouse head position by another operator. Coefficient of repeatability (CR) through Bland-Altman plot method coefficient of variation (COV) and Intraclass correlation coefficient (ICC) was calculated. Intravitreal Aflibercept (1 µg) was administered to Akita eyes and intraocular pressure (IOP) was measured using a tonometer at baseline, day 7, 14, 21 and 28 post-injection. Hurvich and Tsai's criterion was used. RESULTS: Coefficient of repeatability values of repeatability and reproducibility for all quadrants were within limits of agreement. Reliability was excellent (ICC 0.98-0.99) and reproducibility was moderate to excellent (ICC 0.64-0.96). There was a non-significant IOP increase in all Akita eyes at Day 28 (p > 0.05), and significant increase in MT in all quadrants at Day 21 and superior, inferior and temporal quadrants at Day 28 (p < 0.05). CONCLUSION: Laser speckle flowgraphy demonstrates excellent repeatability and moderate to excellent reproducibility in measuring RBF. Intravitreal Aflibercept injection results in a significant increase in MT up to 28 days post-injection without significant increase in IOP.

Comparative Study of Primary SMILE, SMILE Enhancement, and Femtosecond Laser-Assisted LASIK on Higher Order Aberrations and Corneal Densitometry.

PURPOSE: To compare differences in corneal densitometry (CD) and higher order aberrations (HOAs) in eyes that underwent small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) for the treatment of myopia and myopic astigmatism at postoperative months 3, 6, and 12, and to evaluate their changes in a separate cohort of eyes after SMILE enhancement. METHODS: In this prospective, randomized, paired-eye clinical trial, consecutive eligible participants were randomized to undergo SMILE or FS-LASIK in either eye. Main outcome measures were CD and HOAs preoperatively and at 3, 6, and 12 months postoperatively. A separate cohort of consecutive patients who had SMILE and underwent enhancement were also included for comparison. RESULTS: For CD, no significant differences were found between SMILE and FS-LASIK up to month 12. For HOA measured by wavefront aberrometry, both SMILE and FS-LASIK had an increase in total root mean square (RMS) HOAs, spherical aberration (SA), and vertical coma up to month 12. SMILE had an additional increase in vertical quatrefoil, and FS-LASIK had an increase in horizontal coma at month 12. FS-LASIK had higher SA than SMILE, whereas SMILE had higher vertical quatrefoil than FS-LASIK at month 12. Central and posterior zone CD had significantly decreased after SMILE enhancement compared to after primary SMILE up to 2 years after enhancement. RMS HOAs, lower order aberrations, and SA were all increased after SMILE enhancement compared to after primary SMILE. CONCLUSIONS: SMILE induced lower SA but higher vertical quatrefoil than FS-LASIK at 1 year. Both SMILE and FS-LASIK had similar increases in RMS HOAs and vertical coma up to 1 year. There were no differences in CD between both groups. SMILE enhancement additionally had decreased central and posterior CD but greater RMS HOAs and SA compared to primary SMILE. [J Refract Surg. 2024;40(5):e291-e303.].

Moesin as a key cytoskeleton regulator in corneal fibrosis.

PURPOSE: : Corneal fibrosis is the third leading cause of blindness worldwide. α-Smooth muscle actin (SMA), a marker of fibrosis, is closely regulated through an intermediate group of submembrane molecules - cytoskeleton regulators. The purpose of this study was to elucidate the role of specific cytoskeleton regulators in a mouse model of corneal fibrosis. METHODS: : A mouse model of corneal fibrosis was developed using anterior keratectomy (AK) and the topical application of transforming growth factor (TGF)-ß1 (1 µg/ml). The RT² Profiler™ PCR Array for cytoskeleton regulators was used to assay changes in levels of specific members of this class of proteins. Moesin siRNA was delivered into the corneal stroma by iontophoresis in vivo. Transformation of the corneal keratocyte-to-myofibroblast in corneal fibrosis, as defined by the expression of α-SMA, was determined by Western blot. RESULTS: : After AK and topical application of TGF-ß1, moesin was the most highly upregulated gene among 84 cytoskeleton regulator genes; iontophoresing moesin siRNA into the corneal stroma reduced the expression of α-SMA to 0.22-, 0.52-, and 0.31-fold of control at postoperative (PO) day 1, 3, and 5, respectively; also, upregulation of phospho-Smad 2 induced by TGF-ß1 was reduced by moesin siRNA to 0.59-, 0.56-, and 0.31-fold of control and expression of phospho-Smad 3 was reduced to 0.58-, 0.53-, and 0.47-fold of control at the same PO days. CONCLUSIONS: : Moesin may be a potential drug target for inhibiting corneal fibrosis, and the details of moesin-related signaling pathways would be critical for understanding corneal fibrosis.

Endothelial cell loss and graft survival after Descemet's stripping automated endothelial keratoplasty and penetrating keratoplasty.

PURPOSE: We sought to compare endothelial cell (EC) loss and graft survival after Descemet's stripping automated endothelial keratoplasty (DSAEK) and conventional penetrating keratoplasty (PK) in Asian eyes. DESIGN: Retrospective, nested, cohort study. PARTICIPANTS: Consecutive patients who underwent DSAEK or PK with Fuchs' endothelial dystrophy or pseudophakic and aphakic bullous keratopathy (BK) at a single tertiary center from April 1, 2006, to April 1, 2008. METHODS: Clinical data, and donor and recipient characteristics were recorded from our prospective cohort from the Singapore Corneal Transplant Study. MAIN OUTCOME MEASURES: Percent EC loss and graft survival up to 3 years. RESULTS: There were no differences in baseline characteristics of patients comparing DSAEK and PK; there were more patients with BK (n = 141, 68.4%) than Fuchs' dystrophy. Percent EC loss was lower in DSAEK compared with PK at 1 (30 ± 22% vs 37 ± 25%; P = 0.045), 2 (36 ± 23% vs 45 ± 33%; P = 0.018), and 3 years (39 ± 24% vs 47 ± 28%; P = 0.022) postoperatively. Graft survival was comparable (log-rank P = 0.671) between DSAEK and PK at 1 (94% vs 90%), 2 (88% vs 85%), and 3 years (87% vs 85%). CONCLUSIONS: Compared with PK, DSAEK resulted in lower EC loss with comparable cumulative graft survival rates for up to 3 years in patients with Fuchs' dystrophy and BK.

Indications, outcomes, and risk factors for failure in tectonic keratoplasty.

PURPOSE: Outcomes of corneal transplantation for tectonic indications and risk factors for (tectonic and physiologic) graft failure. DESIGN: Retrospective cohort study. PARTICIPANTS: Consecutive patients who underwent keratoplasty for tectonic indications at the Singapore National Eye Centre (SNEC) between January 1, 1991, and December 1, 2009. METHODS: Clinical data and donor and recipient characteristics were recorded and analyzed from subjects in the prospective Singapore Corneal Transplant Study. MAIN OUTCOME MEASURES: (1) Tectonic (anatomic) failure defined as recurrence of corneal melt threatening tectonic integrity and requiring additional corneal grafting within 3 months of the primary procedure. (2) Physiologic failure defined as irreversible change in graft clarity preventing recovery in useful vision in grafts initially clear 2 weeks postoperatively. RESULTS: The mean age of the study cohort (n = 362, 193 male and 169 female subjects) was 51.5 ± 20.2 years, with a mean follow-up of 25.8 ± 18.7 months. Patients underwent penetrating keratoplasty (PK) (n = 142, 39.2%), anterior lamellar keratoplasty (ALK) (n = 127, 35.1%), or a peripheral corneoscleral patch graft (n = 93, 25.7%) most commonly for inflammation (n = 68, 18.8%), trauma (n = 66, 18.2%), or infection (n = 66, 18.2%). Risk factors for tectonic failure (18/362 eyes, 5.0%) were severe lid disease (odds ratio [OR], 6.1; 95% confidence interval [CI], 1.7-22.1; P = 0.006), central ALK (OR, 7.5; 95% CI, 1.8-32.4; P = 0.007), and peripheral grafts (OR, 5.7; 95% CI, 1.1-28.3; P = 0.035). Among anatomically successful central grafts (n = 223), the mean physiological graft survival was 96 months (95% CI, 83-110); Kaplan-Meier probabilities for survival at 10 years were 66.8% for ALK and 44.2% for PK. Active corneal inflammation (hazard ratio [HR], 2.5; 95% CI, 1.4-4.4; P = 0.003) and larger donor and recipient graft sizes of ≥ 9 mm (HR, 17.9; 95% CI, 2.3-140.3; P = 0.006) were risk factors for physiologic graft failure in anatomically successful eyes with central tectonic grafts. CONCLUSIONS: Patients with lid disease, central ALK, and peripheral grafts were at higher risk of anatomic failure. For anatomically successful cases with central tectonic grafts, active corneal inflammation and donor size ≥ 9 mm were risk factors for physiologic failure. In these cases, our results suggest that ALK had better physiologic graft survival outcomes than PK.

Lubricant with gelling agent in treating dry eye in adult Chinese patients.

PURPOSE: To investigate the efficacy of a lubricant eye drop containing gelling agent in adult Chinese dry eye patients. METHODS: This is a prospective, randomized, double-masked, double-arm, parallel, interventional single-site clinical study. Thirty Chinese dry eye patients were randomized into two arms, 15 patients each, receiving lubricant eye drops either containing hydroxypropyl-guar (HP-guar) gelling agent (Systane Ultra) or no gelling agent (Refresh Tears), 1 drop, four times a day for 6 weeks. The main outcome measure was global symptom score (based on severity and frequency of dry eye symptoms on a visual analog scale) at weeks 1, 3, and 6. Secondary outcomes were changes in sectoral corneal fluorescein staining, tear break-up time, and Schirmer's I test results from pretreatment level. RESULTS: Both groups showed significant improvement in symptoms from baseline (p < 0.001). There was no significant difference in the global symptom score at weeks 1, 3, and 6 between the two groups. There was significantly more severe corneal fluorescein staining in the HP-guar group at baseline in the left nasal (p = 0.023) and left inferior (p = 0.046) zones, but no difference in staining was observed between the two arms at weeks 1, 3, and 6. There were no differences in Schirmer's test results or tear break-up time (final and pretreatment) between the two groups (p > 0.05). CONCLUSIONS: Both lubricant eye drops, with or without HP-guar gelling agent, benefit patients in relieving dry eye symptoms. There was no difference in the efficacy of these drugs in terms of improving symptoms and altering objective signs of dry eye.

Effect of corneal stromal lenticule customization on neurite distribution and excitatory property.

Introduction: Refractive stromal lenticules from Small Incision Lenticule Extraction (SMILE), though usually discarded, hold a potential for various ophthalmic applications, including refractive correction, stromal volume expansion, and biomechanical strengthening of the cornea. Objectives: To investigate the effect of lenticule customization on lenticule neurite length profile and the excitatory response (calcium signaling) and the potential of reinnervation. Methods: Human and porcine stromal lenticules were treated by (1) excimer laser reshaping, (2) ultraviolet A-riboflavin crosslinking (CXL), and (3) decellularization by sodium dodecyl sulfate (SDS), respectively. The overall neurite scaffold immuno-positive to TuJ1 (neuron-specific class III ß-tubulin) expression and population of active neurite fragments with calcium response revealed by L-glutamate-induced Fluo-4-acetoxymethyl ester reaction were captured by wide-field laser-scanning confocal microscopy, followed by z-stack image construction. The NeuronJ plugin was used to measure neurite lengths for TuJ1 (NL-TuJ1) and calcium signal (NL-Ca). Reinnervation of lenticules was examined by the ex vivo grafting of chick dorsal root ganglia (DRG) to the decellularized human lenticules. Differences between groups and controls were analyzed with ANOVA and Mann-Whitney U test. Results: The customization methods significantly eliminated neurites inside the lenticules. NL-TuJ1 was significantly reduced by 84% after excimer laser reshaping, 54% after CXL, and 96% after decellularization. The neurite remnants from reshaping and CXL exhibited calcium signaling, indicative of residual excitatory response. Re-innervation occurred in the decellularized lenticules upon stimulation of the grafted chick embryo DRG with nerve growth factor (NGF 2.5S). Conclusion: All of the lenticule customization procedures reduced lenticule neurites, but the residual neurites still showed excitatory potential. Even though these neurite remnants seemed minimal, they could be advantageous to reinnervation with axon growth and guidance after lenticule reimplantation for refractive and volume restoration of the cornea.

The Effects of High Energy Capsulotomy on Aqueous Cytokine Profiles and Pupil Size During Femtosecond Laser-Assisted Cataract Surgery.

PURPOSE: To assess whether aqueous cytokine profiles and pupil size are altered when high capsulotomy energy is used in eyes undergoing femtosecond laser-assisted cataract surgery (FLACS), and if preoperative use of a topical non-steroidal anti-inflammatory drug (NSAID) has an effect on this. METHODS: This prospective study recruited 83 eyes (63 patients) that were allocated to four treatment groups: conventional phacoemulsification (n = 20 eyes); FLACS with 90% capsulotomy energy without NSAID pretreatment (n = 20 eyes); FLACS with 90% capsulotomy energy with NSAID pre-treatment (n = 21 eyes); and FLACS with 150% capsulotomy energy with NSAID pretreatment (n = 22 eyes). Aqueous humor was collected before and after phacoemulsification to assess cytokine profiles. Pupil size was measured before and after laser capsulotomy. RESULTS: FLACS increased aqueous concentrations of pros-taglandin E2 (PGE2), interferon γ (IFN-γ), and interleukin 6 (IL-6) compared to conventional phacoemulsification. However, when increasing capsulotomy energy from 90% to 150% (with topical NSAID pretreatment), there was no significant increase in aqueous concentrations of PGE2 (37.7 ± 21.7 vs 33.6 ± 27.6 pg/mL, P = .99), IFN-γ (3.6 ± 1.1 vs 3.6 ± 0.8 pg/mL, P = .99), or IL-6 (7.1 ± 2.9 vs 6.3 ± 2.4 pg/mL, P = .99). For 90% and 150% capsulotomy energy, there was significant miosis following laser capsulotomy. Increased PGE2 concentration was significantly correlated with a reduction in pupil area (r = -0.58, P < .001) and pupil diameter (r = -0.57, P < .001). However, when a topical NSAID was given preoperatively, there was no difference in the degree of miosis between the 90% and 150% capsulotomy energy groups. CONCLUSIONS: Pretreatment with a topical NSAID prevented a rise in PGE2, IFN-γ, and IL-6 levels and excessive miosis when a higher capsulotomy energy was used. When a topical NSAID is used preoperatively, it is safe to use higher capsulotomy energy settings (with a low pulse energy femtosecond laser system) to achieve a satisfactory capsulotomy. [J Refract Surg. 2022;38(9):587-594.].

The Effects of Donor-Recipient Age and Sex Compatibility in the Outcomes of Deep Anterior Lamellar Keratoplasties.

PURPOSE: Corneal transplantations are the commonest allogenic transplant surgeries performed worldwide. Transplantable grade donor cornea is a finite resource. There is thus an impetus for eye banks to optimize the use of each harvested cornea, and clinicians to minimize the risks of graft rejection and failure. With better survival and lower rejection rates, anterior lamellar keratoplasty has gained popularity as an alternative technique to full-thickness penetrating keratoplasty, for the treatment of corneal stromal diseases. This study evaluated the effects of donor-recipient age- and sex-matching on the outcomes of eyes that had undergone deep anterior lamellar keratoplasty (DALK) surgeries. DESIGN: Observational cross-sectional study (national corneal graft registry data). SUBJECTS: All DALK surgeries performed in a tertiary ophthalmic hospital over an 11-year period. METHODS: To analyse the effects of donor-recipient sex-matching, transplantations were classified as "presumed H-Y incompatible" (male donor to female recipient) or "presumed H-Y compatible" (all other donor-recipient sex combinations). For age-matching, differences in donor and recipient ages were calculated. Cox proportional hazards regressions were used to evaluate the influence of donor-recipient sex-matching and age-matching on graft failure and rejection. MAIN OUTCOME MEASURES: Rates of graft failure and rejection within each group. RESULTS: 401 eyes were included. 271 (67.6%) transplants were presumed H-Y compatible. 29 (7.2%) grafts failed and 9 (2.2%) grafts rejected. There were trends of lower hazard ratios (HRs) in graft failure and rejection in the presumed H-Y compatible group [HRs: 0.59 (95% CI 0.20-1.77, p = 0.34) and 0.93 (95% CI 0.22-3.89, p = 0.926), respectively]. Median difference in age between recipients and donors was 15.0 years (IQR -2.8-34.3). The HRs of graft failure and rejection were not influenced by donor-recipient age [HRs per 1-year increase in age difference: 0.995 (95% CI 0.98-1.01, p = 0.483) and 1.01 (95% CI 0.99-1.03, p = 0.394), respectively]. CONCLUSION: In eyes that had undergone DALK surgeries, no significant influence of donor-recipient sex- or age-matching on graft rejection and failure was observed. Without strong evidence and the limitations of obtaining sample sizes required for an adequately powered study, the benefits of sex- and age-matching of donors and recipients during graft allocation for DALK surgeries is currently inconclusive.

Utilization rate and usage patterns of phakic and pseudophakic donor corneas recovered by the Singapore Eye Bank.

PURPOSE: To compare the utilization rate and usage patterns of pseudophakic and phakic donor corneas recovered by the Singapore Eye Bank. METHODS: Records of local donor corneas recovered by the Singapore Eye Bank from 2012 to 2017 were examined. Corneas that were deemed suitable for clinical use were stratified into phakic and pseudophakic groups. We examined the basic demographic pattern of both groups and the initial type of surgery/ies that the corneas were suitable for based on tissue parameters such as time from harvesting, stromal clarity, the clear central corneal area, the presence of Descemet's membrane tears or defects, and endothelial cell density and quality. We also identified the types of corneal grafts that the corneas were eventually used for; Penetrating Keratoplasty (PK), Anterior Lamellar Keratoplasty (ALK), Endothelial Keratoplasty (EK). Finally, the overall utilization rates for each group were determined. RESULTS: A total of 986 corneas deemed suitable for transplant were analyzed, 908 (92%) were phakic and 78 were pseudophakic (8%). The average age of pseudophakic donor corneas was (65 ± 8 yrs. old) and there was a slight male preponderance for both groups (55%). Age adjusted analysis of pseudophakic corneas showed the endothelial cell density (ECD) (mean: 2327 ± 47.1 cells/mm2) and clear area (mean: 7.0 ± 0.7 mm) were lesser than phakic corneas. The percentage of pseudophakic corneas that were of EK standard (ECD >2500 cells/mm2) were lower compared to phakic corneas (37% and 77% respectively, p < 0.001). There was significant correlation between previous cataract surgery and the endothelial cell count of the donor corneas (p < 0.001), and regression analysis also showed a strong association of ECD with cataract surgery in reference to non-cataract surgery (-478.8 (95% CI-576.9 to -380.7). The overall utilization rate for pseudophakic corneas was 58% compared to that of phakic corneas at 83%. The most common reason for pseudophakic corneas not to be utilized was due to the presence of Descemet's membrane (DM) tears or defects under the main or side port incision created during phacoemulsification (30%). Phakic corneas were used primarily for optical grafts 84% (mainly EK) while pseudophakic corneas were used mostly for therapeutic/tectonic grafts 47% (mainly ALK or patch grafts). CONCLUSION: Compared to phakic donor corneas, pseudophakic corneas generally have lower overall tissue quality leading to lower uptake by surgeons and lower utilization rates. Eye banks must continuously refine their donor acceptance criteria and engage surgeons to optimize utilization of each recovered tissue.

Comparative Study of Long-term Graft Survival Between Penetrating Keratoplasty and Deep Anterior Lamellar Keratoplasty.

PURPOSE: Endothelial failure and immunological graft rejection remain long-term complications leading to late graft failure in penetrating keratoplasty (PK). Deep anterior lamellar keratoplasty (DALK) has emerged as a viable alternative that enables preservation of the host's endothelial cells to eliminate risks of endothelial rejection and failure. The aim of this study was to compare long-term graft survival between PK and DALK. DESIGN: Retrospective clinical cohort study. METHODS: All consecutive primary grafts of DALKs (n = 362) and PKs (n = 307) performed for optical indications in a tertiary eye center from the ongoing, prospective Singapore Corneal Transplant Study. Ten-year graft survival outcomes were compared. Cases in which endothelial pathologies were diagnosed were excluded, as DALK was not performed for such cases. Main outcome measurements were mean graft survival rate. RESULTS: The survival rate for PK was 94.4%, 80.4%, and 72.0% at 1, 5, and 10 years, respectively; and 95.8%, 93.9%, and 93.9% at 1, 5, and 10 years, respectively, for DALK (P = .001). Patients who underwent PK developed more complications of glaucoma (29.3% vs. 11.6%, respectively; P < .001), allograft rejection (16.6% vs. 1.7%, respectively; P < .001), epithelial problems (10.4% vs. 5.5%, respectively; P = .018), and nonimmunological failure (7.8% vs. 1.9%, respectively; P < .001), compared to DALK. Rates of graft failure attributable to rejection (36.7% vs. 5.9%, respectively; P = .015) and endothelial failure (36.7% vs. 5.9%, respectively; P = .015) were lower in DALK. CONCLUSIONS: The 10-year graft survival for primary DALK was superior to that for PK for corneal pathologies with functional endothelium. Primary DALK resulted in fewer post-operative complications and lower rates of graft rejection and failure. This study strengthens the case in favor of performing DALK over PK when possible.

Long-Term Review of Penetrating Keratoplasty: A 20-Year Review in Asian Eyes.

PURPOSE: To review the long-term outcomes of optical, therapeutic and tectonic forms of penetrating keratoplasty over a 20-year period in Asian eyes. DESIGN: Prospective cohort study involving the Singapore Corneal Transplant Study (SCTS). METHODS: All penetrating keratoplasties (PK) performed at the Singapore National Eye Centre (SNEC) from January 1991 to December 2010 were analyzed using records from the computerized database of the SCTS. This database includes preoperative, intraoperative, and postoperative patient data and donor cornea data. Only primary grafts were included. Patient demographics, donor cornea source, indications for grafting, complications, graft survival rate, and causes of graft failure were analyzed. RESULTS: A total of 1,206 primary PKs were performed. The mean age of the patients was 55 years (range: <1-101 years). The overall corneal graft survival rates at 1, 5, 10, 15, and 20 years were 91%, 66.8%, 55.4%, 52%, and 44%, respectively. For optical grafts, pseudophakic bullous keratopathy, postinfectious corneal scarring and thinning and keratoconus were the most common diagnoses. Graft survival for optical grafts was significantly better than therapeutic and tectonic grafts at all time points. Multivariate analysis suggested that a younger donor cornea age and higher donor endothelial cell count are associated with better long-term graft survival for optical grafts. Irreversible allograft rejection and late endothelial failure accounted for more than 60% of graft failures. CONCLUSIONS: Graft survival decreased over time from 91% at 1 year to 44% at 20 years' follow-up. Allograft rejection and late endothelial failure accounted for more than 60% of graft failures.