Optimising graft survival in endothelial keratoplasty for endothelial failure secondary to cytomegalovirus endotheliitis.

BACKGROUND: There is limited information regarding Descemet stripping automated endothelial keratoplasty (DSAEK) for endothelial failure secondary to cytomegalovirus (CMV) endotheliitis. Treatment is difficult with high recurrence rates. We describe a case when systemic valganciclovir therapy is directed by aqueous CMV-DNA levels, leading to good graft survival. FINDINGS: A 59-year-old male with bilateral CMV endotheliitis despite antiviral therapy developed endothelial failure and underwent DSAEK. Prior to surgery, aqueous polymerase chain reaction (PCR) for CMV was repeatedly performed, where CMV-positive episodes were treated with systemic valganciclovir. Monthly aqueous analysis was performed until CMV-DNA was undetectable before DSAEK was performed. Post-operative prophylactic systemic valganciclovir treatment was instituted and switched to topical valganciclovir treatment when aqueous samples were negative for CMV. CONCLUSION: Targeted aqueous sampling for CMV-DNA perioperatively guides antiviral therapy and ensures adequacy of treatment, minimising the duration of systemic valganciclovir therapy to reduce adverse effects of long-term treatment.

Hyperopic refractive correction by LASIK, SMILE or lenticule reimplantation in a non-human primate model.

Hyperopia is a common refractive error, apparent in 25% of Europeans. Treatments include spectacles, contact lenses, laser interventions and surgery including implantable contact lenses and lens extraction. Laser treatment offers an expedient and reliable means of correcting ametropia. LASIK is well-established however SMILE (small-incision lenticule extraction) or lenticule implantation (derived from myopic laser-correction) are newer options. In this study we compared the outcomes of hyperopic LASIK, SMILE and lenticule re-implantation in a primate model at +2D/+4D treatment. While re-implantation showed the greatest regression, broadly comparable refractive results were seen at 3-months with SMILE and LASIK (<1.4D of intended), but a greater tendency to regression in +2D lenticule reimplantation. Central corneal thickness showed greater variation at +2D treatment, but central thickening during lenticule reimplantation at +4D treatment was seen (-17± 27µm LASIK, -45 ± 18µm SMILE and 28 ± 17µm Re-implantation; p <0.01) with expected paracentral thinning following SMILE. Although in vivo confocal microscopy appeared to show higher reflectivity in all +4D treatment groups, there were minimal and inconsistent changes in inflammatory responses between modalities. SMILE and lenticule re-implantation may represent a safe and viable method for treating hyperopia, but further optimization for lower hyperopic treatments is warranted.

Retreatment strategies following Small Incision Lenticule Extraction (SMILE): In vivo tissue responses.

With any refractive correction, including Small Incision Lenticule Extraction (SMILE), there may be a residual refractive error that requires a retreatment. Here, we investigated the tissue responses following various retreatment procedures in a rabbit model of SMILE. All rabbits underwent a -6.00D correction with SMILE. Two weeks later, they underwent -1.00D enhancement by: (i) VisuMax Circle, followed by excimer ablation (S+C); (ii) secondary SMILE anterior to the primary procedure (S+SE); or (iii) surface ablation (S+P), and were examined for 28 days. S+P induced corneal edema and haze, and more CD11b- (23±6 cells) and TUNEL-positive (36±4 cells) cells in the central stromal superficial layers early post-operatively (p<0.001 compared to other procedures). The corneas appeared normal on day 28 after S+P, but had a lower number of keratocytes near the laser ablated plane compared to other procedures. S+SE and S+C did not induce corneal haze and resulted similar level of fibronectin. However, S+C resulted in more inflammatory (10±2 cells; p = 0.001) and apoptotic cells (25±2 cells; p<0.001) compared to S+SE (7±1 inflammatory cells and 21±3 apoptotic cells) early post-operatively. In conclusion, each SMILE retreatment method resulted in unique tissue responses. S+SE offers advantages, such as minimal inflammation and cell death, as well as maintaining a 'flap-less' surgery, over other procedures. However, depending on the degree of enhancement, the lenticule may become too thin to be extracted and the procedure becomes more difficult to perform than S+C and S+P. S+P can maintain corneal integrity by avoiding flap creation and is technically more simple to perform than the others, but the surgery needs to be supplemented with mitomycin-C in order to reduce inflammation and modulate better wound healing.

Amphiphilic xanthones as a potent chemical entity of anti-mycobacterial agents with membrane-targeting properties.

Tuberculosis (TB) remains a deadly disease and infects one-third of the world's population. Given the low success rates encountered in clinical development, there is an urgent need to identify structurally novel antimicrobials for tuberculosis. The present report details the anti-mycobacterial activities, structure-activity relationships (SARs) and mechanism of action of amphiphilic xanthone derivatives. The xanthones exhibited potent MIC, rapid time-kill and no cross-resistance with the current anti-TB drugs. Evidence is presented that these compounds disrupted the inner membrane and led to ATP depletion. Amphiphilic xanthone derivatives exhibited superior metabolic stability, low cytotoxicity and low activity against the common cytochrome P450. Compound 5 was selected for an in vivo pharmacokinetic study. Its bioavailability at an oral dose of 2 mg/kg was 15%. The xanthones thuse provide valuable insight for the development of a new class of membrane targeting antimycobacterial agents that may assist in overcoming the limitations of the current TB medications.

Histological features of Cytomegalovirus-related corneal graft infections, its associated features and clinical significance.

AIM: To describe the histological features of ITALIC! Cytomegalovirus (CMV)-related corneal graft infections, its associated features and clinical significance. METHODS: This was a retrospective histological study of 48 consecutive cases of failed repeat penetrating keratoplasty cases with a clinical diagnosis of allograft rejection from 2011 to 2013. CMV infection was confirmed with CMV antibody immunohistochemistry (IHC) and electron microscopy. Additional CD163 and CD68 IHCs for macrophages were also performed. Clinical data and previous graft histology were then reviewed. RESULTS: Mean incidence of CMV infection in corneal graft rejection buttons was 6.3% per year. 3/48 graft buttons were CMV antibody positive. Histological features of CMV graft infection include: (1) stromal keratocytes with cytopathic changes; (2) lack of inflammation, only occasional macrophages present and (3) absence of vascularisation. None of the patients had a history of active CMV infection. CONCLUSION: CMV infection is not limited as endotheliitis, but extends into the corneal stroma, and is a potential reservoir for graft infection, especially in partial thickness endothelial surgery. Clinical features are often non-specific, although glaucoma was present in our patients. CMV-infected grafts showed CD163-positive M2 macrophages in close association with the infected keratocytes, suggesting that the macrophage may be important in CMV graft infection. Histological examination with CMV IHC is a useful method to detect CMV infection postoperatively. Post penetrating keratoplasty, CMV systemic treatment with valganciclovir can prevent graft infection and failure. Boston keratoprosthesis may be a potential alternative surgery in active CMV infections that obviates the need for systemic therapy.

Nonpeptidic Amphiphilic Xanthone Derivatives: Structure-Activity Relationship and Membrane-Targeting Properties.

We recently reported the bioinspired synthesis of a highly potent nonpeptidic xanthone, 2c (AM-0016), with potent antibacterial activity against MRSA. Herein, we report a thorough structure-activity relationship (SAR) analysis of a series of nonpeptidic amphiphilic xanthone derivatives in an attempt to identify more potent compounds with lower hemolytic activity and greater membrane selectivity. Forty-six amphiphilic xanthone derivatives were analyzed in this study and structurally classified into four groups based on spacer length, cationic moieties, lipophilic chains, and triarm functionalization. We evaluated and explored the effects of the structures on their membrane-targeting properties. The SAR analysis successfully identified 3a with potent MICs (1.56-3.125 µ/mL) and lower hemolytic activity (80.2 µg/mL for 3a versus 19.7 µg/mL for 2c). Compound 3a displayed a membrane selectivity of 25.7-50.4. Thus, 3a with improved HC50 value and promising selectivity could be used as a lead compound for further structural optimization for the treatment of MRSA infection.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis--A Comprehensive Review and Guide to Therapy. I. Systemic Disease.

The intent of this review is to comprehensively appraise the state of the art with regard to Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to the ocular surface complications and their management. SJS and TEN represent two ends of a spectrum of immune-mediated, dermatobullous disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. The widespread keratinocyte death seen in SJS/TEN is rapid and irreversible, and even with early and aggressive intervention, morbidity is severe and mortality not uncommon. We have divided this review into two parts. Part I summarizes the epidemiology and immunopathogenesis of SJS/TEN and discusses systemic therapy and its possible benefits. We hope this review will help the ophthalmologist better understand the mechanisms of disease in SJS/TEN and enhance their care of patients with this complex and often debilitating disease. Part II (April 2016 issue) will focus on ophthalmic manifestations.

Graft failure and intraocular pressure control after keratoplasty in iridocorneal endothelial syndrome.

PURPOSE: To describe and compare graft survival and intraocular pressure (IOP) control after penetrating keratoplasty (PK) and Descemet stripping automated endothelial keratoplasty (DSAEK) in eyes with iridocorneal endothelial (ICE) syndrome. DESIGN: Retrospective case series. METHODS: Multicenter study conducted at the Singapore National Eye Centre (SNEC) and Price Vision Group. Twenty-nine consecutive eyes with ICE syndrome that underwent keratoplasty between 1991 and 2011 were identified from the SNEC transplant database and Price Vision Group patient database and the following data extracted: demographics, graft failure, IOP indices, and glaucoma treatment pre- and postkeratoplasty. The main outcome measures were graft failure and need for additional IOP-lowering treatment after keratoplasty. RESULTS: The mean follow-up duration was 7.0 ± 4.9 years in the PK group (n = 17) and 4.0 ± 2.6 years in the DSAEK group (n = 12). After a mean of 4.1 ± 3.1 years, 37.9% of grafts (11/29) failed: 7 PK compared to 4 DSAEK (P = .72). The graft failure rate was 50% in eyes with prekeratoplasty glaucoma surgery vs 31.6% in those without (P = .43). Additional glaucoma treatment was required in 37.9% of eyes (11/29): 41.2% of PK eyes and 50% of DSAEK eyes (P = .28) Eyes that had undergone glaucoma surgery before keratoplasty were less likely to require escalation of IOP-lowering therapy postkeratoplasty (9.1% vs 50%, P = .03). CONCLUSIONS: One-third of grafts failed after keratoplasty for ICE syndrome at a mean duration of 4 years and additional IOP-lowering treatment was required in 37.9%. Both PK and DSAEK had similar outcomes with regard to graft failure and IOP control.

Postoperative ocular higher-order aberrations and contrast sensitivity: femtosecond lenticule extraction versus pseudo small-incision lenticule extraction.

PURPOSE: To evaluate and compare changes in contrast sensitivity and ocular higher-order aberrations (HOAs) after femtosecond lenticule extraction (FLEx) and pseudo small-incision lenticule extraction (SMILE). SETTING: Singapore National Eye Centre, Singapore. DESIGN: Retrospective case series. METHOD: Patients had femtosecond lenticule extraction (Group 1) or pseudo small-incision lenticule extraction (Group 2) between March 2010 and December 2011. The main outcome measures were manifest refraction, HOAs, and contrast sensitivity 1, 3, 6, and 12 months postoperatively. RESULTS: Fifty-two consecutive patients (102 eyes) were recruited, 21 patients (42 eyes) in Group 1 and the 31 patients (60 eyes) in Group 2. The uncorrected and corrected distance visual acuities were significantly better in Group 2 than in Group 1 at 12 months (P = .032). There was no significant increase in 3rd- or 4th-order aberrations at 1 year and no significant difference between the 2 groups preoperatively or postoperatively. At 1 year, there was a significant increase in mesopic contrast sensitivity in Group 2 at 1.5 cycles per degree (cpd) (P = .008) that was not found in Group 1, and photopic contrast sensitivity at 6.0 cpd was higher in Group 2 (P = .027). CONCLUSIONS: These results indicate that refractive lenticule extraction is safe and effective with no significant induction of HOAs or deterioration in contrast sensitivity at 1 year. Induction of HOAs was not significantly different between both variants of refractive lenticule extraction. However, there was significant improvement in photopic contrast sensitivity after pseudo small-incision lenticule extraction, which persisted through 1 year. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Propagation of human corneal endothelial cells: a novel dual media approach.

Corneal endothelium-associated corneal blindness is the most common indication for corneal transplantation. Restorative corneal transplant surgery is the only option to reverse the blindness, but a global shortage of donor material remains an issue. There are immense clinical interests in the development of alternative treatment strategies to alleviate current reliance on donor materials. For such endeavors, ex vivo propagation of human corneal endothelial cells (hCECs) is required, but current methodology lacks consistency, with expanded hCECs losing cellular morphology to a mesenchymal-like transformation. In this study, we describe a novel dual media culture approach for the in vitro expansion of primary hCECs. Initial characterization included analysis of growth dynamics of hCECs grown in either proliferative (M4) or maintenance (M5) medium. Subsequent comparisons were performed on isolated hCECs cultured in M4 alone against cells expanded using the dual media approach. Further characterizations were performed using immunocytochemistry, quantitative real-time PCR, and gene expression microarray. At the third passage, results showed that hCECs propagated using the dual media approach were homogeneous in appearance, retained their unique polygonal cellular morphology, and expressed higher levels of corneal endothelium-associated markers in comparison to hCECs cultured in M4 alone, which were heterogeneous and fibroblastic in appearance. Finally, for hCECs cultured using the dual media approach, global gene expression and pathway analysis between confluent hCECs before and after 7-day exposure to M5 exhibited differential gene expression associated predominately with cell proliferation and wound healing. These findings showed that the propagation of primary hCECs using the novel dual media approach presented in this study is a consistent method to obtain bona fide hCECs. This, in turn, will elicit greater confidence in facilitating downstream development of alternative corneal endothelium replacement using tissue-engineered graft materials or cell injection therapy.

Refractive lenticule extraction: transition and comparison of 3 surgical techniques.

PURPOSE: To describe the transition and outcomes of 3 refractive lenticule extraction (ReLEx) techniques: femtosecond lenticule extraction (FLEx), small-incision lenticule extraction (SMILE), and pseudo small-incision lenticule extraction. SETTING: Singapore National Eye Center, Singapore. DESIGN: Prospective comparative case series. METHODS: Refractive lenticule extraction was performed between March 1, 2010, and November 1, 2012, using the Visumax 500 kHz femtosecond laser system. The main outcome measures were the refractive efficacy, predictability, and safety over 12 months. RESULTS: The study enrolled 88 eyes. All 3 refractive lenticule extraction techniques yielded good refractive outcomes and stability over 12 months. Three months postoperatively, the mean overall efficacy index of refractive lenticule extraction was 0.89±0.22 (SD), with 95.5% of eyes attaining an uncorrected distance visual acuity (UDVA) of better than 20/40 and 60.2% of better than 20/20. Of all eyes, 95.5% were within ±1.00 diopter (D) and 78.4% within ±0.50 D of the attempted correction. The mean overall safety index was 1.06±0.17. At 3 months, all small-incision lenticule extraction eyes and 96.7% of pseudo small-incision lenticule extraction eyes had a UDVA of 20/40 or better, while femtosecond lenticule extraction eyes had a lower efficacy index (87.0%). However, efficacy was comparable in all 3 groups by 12 months (mean 0.87±0.04 [standard error of the mean]; P=1.00). CONCLUSION: The efficacy, safety, and predictability profiles of the 3 refractive lenticule extraction techniques were good over a 12-month follow-up. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Nerve growth factor expression and nerve regeneration in monkey corneas after LASIK.

PURPOSE: To determine whether changes in cornea nerve growth factor (NGF) protein and gene expression correlate with corneal nerve regeneration after LASIK in rhesus monkeys. METHODS: Ten rhesus monkeys underwent randomly assigned LASIK procedures to correct -8.0 diopters of myopia in both eyes and two additional monkeys (with no surgery) served as controls. The central corneas of the experimental animals were excised 3 and 7 days and 1, 3, and 6 months after the surgery. Nerve regeneration, NGF mRNA, and protein expression were analyzed by gold chloride staining, real-time polymerase chain reaction, and enzyme-linked immune sorbent assay analysis, respectively. RESULTS: Compared to controls, the LASIK-treated animals had a significantly diminished nerve plexus in the sub-basal region of the cornea at all times after the surgery (P < .001). NGF protein levels decreased significantly on days 3 and 7 after LASIK (P < .001), but returned to control levels 1 month later. NGF mRNA levels increased 5.4-fold on day 3 after the surgery (P < .001), then reduced to two-fold (P < .05) above control levels on day 7 and were back to normal at 3 months and beyond. After LASIK, the changes of early NGF protein and NGF mRNA levels correlated with the density of the corneal nerve plexuses. CONCLUSIONS: The results showed that the LASIK procedure in non-human primates was associated with changes in NGF protein and mRNA levels in the cornea. Such changes may be related to the initiation of nerve regeneration and the final recovery of nerve plexuses in the cornea.

Comparative study of nJ- and µJ-energy level femtosecond lasers: evaluation of flap adhesion strength, stromal bed quality, and tissue responses.

PURPOSE: To compare flap adhesion strength, stromal bed quality, and tissue responses after flap preparation using nJ- and µJ-energy level femtosecond lasers. METHODS: All corneal flaps were created by either VisuMax laser (µJ-energy level) or femto-LDV (nJ-energy level). Flap adhesion strength in the rabbits was measured with a tension meter 1 and 2 months postoperatively. To investigate tissue responses to laser delivery, immunofluorescence staining and TUNEL assay were performed 4 and 24 hours postoperatively. To assess flap bed smoothness, human donor corneas were used. Surface irregularities were graded based on scanning electron microscopy results. RESULTS: The flap adhesion strength in the VisuMax group at month 1 and 2 was 16.95 ± 1.45 kPa and 18.33 ± 1.81 kPa, respectively; and 12.31 ± 4.15 kPa and 13.85 ± 4.78 kPa in the LDV group, respectively. No significant difference was found between the groups. Fibronectin and apoptotic cells were largely absent at the central incision site in the LDV group, but were present in the VisuMax group. The smoothness of flap beds appeared similar for both groups. An observer scored the VisuMax group 8.00 ± 1.00 and the LDV group 7.33 ± 0.58 (P = 0.387). CONCLUSIONS: The flap adhesion strength increased over time after treatment with both lasers. The nJ-energy pulses produced minimal wound healing reaction and apoptotic cells along the incision plane. The application of an nJ-energy laser, which can incise the cornea without inducing significant damage to cells and wound healing reaction, offers great potential at reducing scarring following incisional laser stromal surgery.

Patient and surgeon experience during laser in situ keratomileusis using 2 femtosecond laser systems.

PURPOSE: To describe the subjective experience of patients and surgeons during laser in situ keratomileusis (LASIK) using the Intralase 60 kHz or the Visumax 500 kHz femtosecond laser. SETTING: Singapore National Eye Centre, Singapore. DESIGN: Prospective randomized clinical study. METHODS: In myopic patients, LASIK was performed with the corneal flap created using the 60 kHz laser in 1 eye and the 500 kHz laser in the contralateral eye. Postoperatively, patients completed a standardized validated questionnaire about their subjective intraoperative experiences (eg, light perception, pain, fear). Surgeons reported their intraoperative experiences and preferences. RESULTS: Loss of light perception occurred in 50.0% of 60 kHz laser cases and 0% of 500 kHz laser cases during docking and in 63.0% and 0% of cases, respectively, during laser flap creation (P < .0001). The mean pain score with the 60 kHz laser was significantly higher during docking (P < .0001) but not during laser flap cutting (P = .006). Subconjunctival hemorrhage occurred in 67.4% of eyes with the 60 kHz laser and in 2.2% of eyes with the 500 kHz laser (P < .0001). The 500 kHz laser was preferred by 78.3% of patients, while 21.7% preferred the 60 kHz laser (P < .0001). The surgeons preferred the 60 kHz laser in 50.0% of cases and the 500 kHz laser in 8.7% (P < .0001); 41.3% had no preference. CONCLUSIONS: Patients preferred surgery with the 500 kHz laser with no loss of light perception, less pain, less fear, and less subconjunctival hemorrhage. Surgeons preferred the 60 kHz laser.

Vitreoretinal complications and vitreoretinal surgery in osteo-odonto-keratoprosthesis surgery.

PURPOSE: To describe the indications for and approaches to vitreoretinal surgery in patients with osteo-odonto-keratoprosthesis (OOKP). DESIGN: Retrospective case series. METHODS: This was a retrospective review of all patients who had undergone OOKP surgery between 2003 and 2012 at our center. OOKP procedures were performed for severe ocular surface disease according to the indications and techniques described in the patient demographics of the Rome-Vienna Protocol. Indications for retinal surgery, surgical outcomes, and intraoperative and postoperative complications were documented. Operative techniques were reviewed from the surgical records, and any subsequent surgeries were also recorded. RESULTS: Thirty-six patients underwent OOKP, and retinal surgery was indicated in 13 (36%). The indications for and approaches to surgery were retinal detachment repair using an Eckardt temporary keratoprosthesis; assessment of retina and optic nerve health prior to OOKP surgery, using either a temporary keratoprosthesis or an endoscope; endoscopic cyclophotocoagulation for intractable glaucoma; endoscopic trimming of a retroprosthetic membrane; or vitrectomy for endophthalmitis with visualization through the OOKP optic using the binocular indirect viewing system. In all cases, retinal surgical aims were achieved with a single procedure. Postoperative vitreous hemorrhage occurred in 16 patients (44%), but all resolved spontaneously. CONCLUSIONS: OOKPs represent the last hope for restoration of vision in severe ocular surface disease, and the retinal surgeon is frequently called upon in the assessment and management of these patients. Temporary keratoprostheses and endoscopic vitrectomies are valuable surgical tools in these challenging cases, improving functional outcomes without compromising OOKP success.

LASIK following small incision lenticule extraction (SMILE) lenticule re-implantation: a feasibility study of a novel method for treatment of presbyopia.

Presbyopia remains a major visual impairment for patients, who have previously undergone laser refractive correction and enjoyed unaided distance vision prior to the onset of presbyopia. Corneal stromal volume restoration through small incision lenticule extraction (SMILE) lenticule re-implantation presents an opportunity for restoring the patients' non-dominant eye to previous low myopia to achieve a monovision. In this study, we investigated the feasibility of performing LASIK after lenticule re-implantation as a method to create presbyopic monovision. A -6.00D SMILE correction was performed in 9 rabbit eyes. The lenticules were cryopreserved for 14 days and re-implanted. Five weeks later, 3 of these eyes underwent LASIK for -5.00D correction (RL group); 3 underwent LASIK flap creation, which was not lifted (RN); and no further procedures were performed on the remaining 3 eyes. These groups were compared with 3 eyes that underwent standard LASIK for a -5.00D correction (LO); 3 that underwent creation of non-lifted flap (LN); and 3 non-operated eyes. Rabbits were euthanized 1 day post-surgery. Tissue responses were analyzed by immunohistochemistry, slit lamp and in vivo confocal microscopy (IVCM). Intrastromal irregularities and elevated reflectivity levels of the excimer-ablated plane were observed on slit lamp and IVCM, respectively in the RL group. The results were comparable (P = 0.310) to IVCM findings in the LO group. RL and LO groups showed similar fibronectin expression levels, number of CD11b-positive cells (P = 0.304) and apoptotic cells (P = 0.198). There was no difference between the RN and LN groups in reflectivity levels (P = 0.627), fibronectin expression levels, CD11b-positive cells (P = 0.135) and apoptotic cells (P = 0.128). LASIK can be performed following lenticule re-implantation to create presbyopic monovision. The tissue responses elicited after performing LASIK on corneas that have undergone SMILE and subsequent lenticule re-implantation are similar to primary procedure.

De novo ocular hypertension after Descemet stripping endothelial keratoplasty: comparative 3-year incidence, risk factors, and outcomes.

OBJECTIVE: To compare the 3-year incidence of de novo ocular hypertension (OHT) after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK). For DSAEK, to evaluate predictors for OHT and 2-year outcomes after OHT development. METHODS: This was a review of the prospective Singapore Corneal Transplant Study at a single tertiary referral center. Consecutive DSAEKs and PKs for Fuchs' endothelial dystrophy (FED) and pseudophakic bullous keratopathy (PBK) in eyes without pre-existing glaucoma were analyzed. OHT incidence after DSAEK and PK were compared using Kaplan-Meier survival analysis, and OHT risk factors identified using Cox proportional regression. OHT was defined: intraocular pressure (IOP) ≥ 24 mmHg or ≥ 10 mmHg from baseline. Secondary outcomes 2 years after OHT development in DSAEK were rates of glaucoma medical therapy failure, IOP success, graft failure and rejection, and best-spectacle corrected visual acuity (BSCVA). RESULTS: There were 108 (96.4%) DSAEKs and 216 (96%) PKs. The 1-, 2- and 3-year de novo OHT incidence was not significantly different between DSAEK (36.1%, 47.2%, 47.2%, respectively) and PK (35.7%, 44.9%, 45.8%, respectively; P = 0.914). OHT incidence did not differ in subgroup analyses of multiple clinical variables (P > 0.1). OHT predictors after DSAEK were: fellow eye glaucoma (hazard ratio [HR] 3.20, P = 0.004), age <60 years (HR 2.41, P = 0.016), concurrent goniosynechiolysis (HR 3.29, P = 0.021), post-graft complications or procedures (HR 2.85, P = 0.006). Two years after OHT onset, 29.7% of DSAEKs failed glaucoma medical therapy requiring trabeculectomy. Complete and qualified IOP success was achieved in 23.5% and 76.5%, respectively. Graft failure developed in 9.8% and graft rejection in 5.9%. At 6 months, 1, and 2 years from OHT onset, 86.3%, 88.3%, and 92.1% achieved BSCVA 20/40, respectively. CONCLUSION: DSAEK and PK have comparable OHT risks. A significant 30% of DSAEK eyes with OHT require filtration surgery. Effective IOP control and good graft and visual outcomes are achieved with treatment.

Descemet stripping automated endothelial keratoplasty with a donor insertion device: clinical results and complications in 100 eyes.

PURPOSE: To study the clinical outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) with the EndoGlide donor insertion device. DESIGN: Retrospective interventional case series. METHODS: We included 100 eyes that underwent DSAEK for Fuchs endothelial dystrophy or pseudophakic bullous keratopathy (PBK) at a single institution. Eyes with anterior segment pathology or previous intraocular surgery (except for uncomplicated cataract surgery) were excluded. Preoperative data included visual acuity and donor endothelial cell density by specular microscopy. The main outcome measures were postoperative best spectacle-corrected visual acuity (BSCVA) and endothelial cell loss at 3, 6, and 12 months. RESULTS: There were 59 eyes with Fuchs dystrophy and 41 eyes with PBK. In eyes without vision-limiting pathology, the median postoperative BSCVA was consistently 20/40 (range 20/20-20/400) at 3 months (n = 61 eyes), 6 months (n = 55 eyes), and 12 months (n = 48 eyes). Endothelial cell loss was 13.7% at 3 months (n = 57), 13.5% at 6 months (n = 61), and 14.9% at 12 months (n = 53). Primary graft failure occurred in 1 eye, attributable to incorrect use of the insertion device. Two eyes with complete donor dislocation were rebubbled successfully. The most common complication was glaucoma/ocular hypertension in 29 eyes (34.1%) without prior glaucoma and treatment escalation in 6 eyes (40.0%) with prior glaucoma. Of the 78 eyes with 12 months follow-up, 2 (2.6%) developed endothelial rejection, and 1 (1.3%) subsequently failed. CONCLUSIONS: The use of this donor insertion device during DSAEK demonstrates good outcomes and potentially low endothelial cell loss at up to 12 months after surgery.

Comparison of efficacy and safety of laser in situ keratomileusis using 2 femtosecond laser platforms in contralateral eyes.

PURPOSE: To compare the efficacy, predictability, and refractive outcomes of laser in situ keratomileusis (LASIK) using 2 femtosecond platforms for flap creation. SETTING: Multisurgeon single center. DESIGN: Clinical trial. METHODS: Bilateral femtosecond LASIK was performed using the Wavelight Allegretto Eye-Q 400 Hz excimer laser system. The Visumax femtosecond platform (Group 1) was used to create the LASIK flap in 1 eye, while the Intralase femtosecond platform (Group 2) was used to create the LASIK flap in the contralateral eye. The preoperative, 1-month, and 3-month postoperative visual acuities, refraction, and contrast sensitivity in the 2 groups were compared. RESULTS: The study enrolled 45 patients. Three months after femtosecond LASIK, 79.5% of eyes in Group 1 and 82.1% in Group 2 achieved an uncorrected distance visual acuity of 20/20 (P=.808). The mean efficacy index was 0.97 in Group 1 and 0.98 in Group 2 at 3 months (P=.735); 89.7% of eyes in Group 1 and 84.6% of eyes in Group 2 were within ± 0.50 diopter of emmetropia at 3 months (P=.498). No eye in either group lost more than 2 lines of corrected distance visual acuity. The mean safety index at 3 months was 1.11 in Group 1 and 1.10 in Group 2 (P=.570). CONCLUSION: The results of LASIK with both femtosecond lasers were similar, and both platforms produced efficacious and predictable LASIK outcomes. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Comparison of four different VisuMax circle patterns for flap creation after small incision lenticule extraction.

PURPOSE: To compare four different Circle patterns for flap creation after small incision lenticule extraction (SMILE). METHODS: SMILE was performed on six rabbits. Twenty-eight days after the initial procedure, corneal flaps were created using Circle patterns. Rabbits were divided into four groups (patterns A, B, C, and D). Pattern A creates a circular side cut to meet the cap cut within the clearance zone (outside of the optical zone). Patterns B, C, and D create a lamellar ring posterior, anterior, and at the same depth, respectively, to the cap to meet the cap cut in the clearance zone with the help of a junction cut. Difficulty of flap lift was graded from 1 (easiest) to 5 (most difficult). The bed quality was assessed by scanning electron microscopy. RESULTS: Flaps created by patterns A and D were the easiest to lift (grade 2). The resulting flap bed was smooth and undisrupted. However, pattern A resulted in a reduced re-treatment area. Flaps created by pattern B were the most difficult to lift (grade 4). The stromal dissection was difficult in an attempt to ascertain the original optical zone from the lamellar ring, placed posterior. Flaps produced by pattern C were easy to lift, with minor intrastromal resistance experienced during the lifting process (grade 3). The transition between the lamellar ring and cap cut was hardly discernible in pattern C-treated corneas. CONCLUSIONS: Pattern D, a lamellar ring adjacent to the cap cut, was the most optimal to be used for flap creation in cases of SMILE re-treatment.