A tissue-engineered human trabecular meshwork hydrogel for advanced glaucoma disease modeling.

Abnormal human trabecular meshwork (HTM) cell function and extracellular matrix (ECM) remodeling contribute to HTM stiffening in primary open-angle glaucoma (POAG). Most current cellular HTM model systems do not sufficiently replicate the complex native three dimensional (3D) cell-ECM interface, limiting their use for investigating POAG pathology. Tissue-engineered hydrogels are ideally positioned to overcome shortcomings of current models. Here, we report a novel biomimetic HTM hydrogel and test its utility as a POAG disease model. HTM hydrogels were engineered by mixing normal donor-derived HTM cells with collagen type I, elastin-like polypeptide and hyaluronic acid, each containing photoactive functional groups, followed by UV crosslinking. Glaucomatous conditions were induced with dexamethasone (DEX), and effects of the Rho-associated kinase (ROCK) inhibitor Y27632 on cytoskeletal organization and tissue-level function, contingent on HTM cell-ECM interactions, were assessed. DEX exposure increased HTM hydrogel contractility, f-actin and alpha smooth muscle actin abundance and rearrangement, ECM remodeling, and fibronectin deposition - all contributing to HTM hydrogel condensation and stiffening consistent with glaucomatous HTM tissue behavior. Y27632 treatment produced precisely the opposite effects and attenuated the DEX-induced pathologic changes, resulting in HTM hydrogel relaxation and softening. For model validation, confirmed glaucomatous HTM (GTM) cells were encapsulated; GTM hydrogels showed increased contractility, fibronectin deposition, and stiffening vs. normal HTM hydrogels despite reduced GTM cell proliferation. We have developed a biomimetic HTM hydrogel model for detailed investigation of 3D cell-ECM interactions under normal and simulated glaucomatous conditions. Its bidirectional responsiveness to pharmacological challenge and rescue suggests promising potential to serve as screening platform for new POAG treatments with focus on HTM biomechanics.

Long-term Outcomes in Fellow Eyes Comparing DSAEK and DMEK for Treatment of Fuchs Corneal Dystrophy.

PURPOSE: To compare the long-term results of Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK) in fellow eyes for treatment of Fuchs endothelial corneal dystrophy. METHODS: This study is a 2-centered, retrospective case series of 64 patients (128 eyes) with DSAEK followed by DMEK. The main outcomes measured were best spectacle-corrected visual acuity (BSCVA) and duration of time to achieve BSCVA as well as eye preference. RESULTS: Preoperative median logarithm of the minimum angle of resolution (logMAR) BSCVA was similar in eyes receiving DMEK 0.36 ± 0.26 and DSAEK 0.42 ± 0.34 (P = .266). The average follow-up time needed for the DMEK eyes to achieve BSCVA was faster than that of DSAEK (277 days vs 490 days, P = .0014). With long-term follow-up, the BSCVA of the DMEK eyes [0.09 ± 0.10 logMAR] and DSAEK eyes [0.11 ± 0.16 logMAR] did not show a statistically significant difference (P = .069). Twenty-two of the 64 preferred the DMEK eye, 17 patients preferred the DSAEK eye (P = .423), and 25 patients did not have a preference. In the DMEK group, the average spherical equivalent was -0.08 compared with the DSAEK group at 0.06 (P = .2854). CONCLUSION: In our fellow eye study with long-term follow-up, DMEK and DSAEK had comparable levels of BSCVA and patient satisfaction. The DMEK eyes reached their BSCVA sooner, whereas the DSAEK eyes improved over a longer time frame. A greater number of patients had 20/25 and 20/20 vision in the DMEK group; however, the difference was not statistically significant. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Calculation of intraocular lens power using Orbscan II quantitative area topography after corneal refractive surgery.

PURPOSE: To present the prospective application of the Orbscan II central 2-mm total-mean corneal power obtained by quantitative area topography in intraocular lens (IOL) calculation after refractive surgery. METHODS: Calculated and achieved refraction and the difference between them were studied in 77 eyes of 61 patients with previous radial keratotomy (RK), RK and additional surgeries, myopic LASIK, myopic photorefractive keratectomy (PRK), or hyperopic LASIK who underwent phacoemulsification without complications in 3 eye centers. All IOL calculations used the average from the central 2-mm Orbscan II total-mean power of maps centered on the pupil without the use of previous refractive data. Six IOL styles implanted within the bag were used. RESULTS: Using the SRK-T formula, the overall calculated refraction was -0.64+/-0.93 diopters (D). The overall achieved spherical equivalent refraction (-0.52+/-0.79 D; range: -3.12 to 1.25 D; 95% confidence interval [CI]: -0.70/-0.34 D) was +/-0.50 D in 53% of eyes, +/-1.00 D in 78% of eyes, and +/-2.00 D in 99% of eyes. The overall difference between the calculated and achieved refraction (0.12+/-0.93 D, P=.27; range: -2.18 to 2.62 D; 95% CI: 0.09/0.33 D) was +/-0.50 D in 39% of eyes, +/-1.00 D in 77% of eyes, and +/-2.00 D in 96% of eyes. This difference was +/-1.00 D in 77% of eyes with RK (P=.70), 82% of eyes with myopic LASIK (P=.34), and 90% of eyes with myopic PRK (P=.96). In eyes with RK followed by LASIK, a trend toward undercorrection was noted (P=.03). In eyes with hyperopic LASIK, a trend toward overcorrection was noted (P=.005). CONCLUSIONS: In eyes with previous corneal refractive surgery, IOL power calculation can be performed with reasonable accuracy using the Orbscan II central 2-mm total-mean power. This method had better outcomes in eyes with previous RK, myopic LASIK, and myopic PRK than in eyes with hyperopic LASIK or RK with LASIK.

Photorefractive keratectomy for treatment of flap complications in laser in situ keratomileusis.

PURPOSE: To present the results of photorefractive keratectomy (PRK) for treatment of laser in situ keratomileusis (LASIK) flap complications. METHODS: Compilation of case reports through solicitation on Kera-net, an Internet surgery discussion site. RESULTS: PRK was performed on 13 patients from 2 weeks to 6 months after LASIK flap complications. The technique used for the PRK varied. Epithelial removal was performed using no-touch phototherapeutic keratectomy (PTK) in six of the 13 patients and manual debridement in the other seven patients. A dilute solution of 20% ethanol was used to facilitate manual debridement in five of the seven patients. In two of these five patients, the epithelium was replaced as in laser-assisted subepithelial keratomileusis (LASEK). A solution of 0.02% mitomycin C was used after laser ablation to prevent haze formation in three patients. After an average 7 months of follow-up, uncorrected visual acuity was 20/20 in six patients, 20/25 in four patients, and 20/30 in two patients. The visual acuity in one patient was 20/80, purposely left undercorrected for monovision. Best spectacle-corrected visual acuity was 20/20 in 10 of 13 patients. Three patients were 20/25, losing one line of best spectacle-corrected visual acuity. On slit-lamp examination, at last follow-up appointment, stromal haze was graded from trace to none in all patients. CONCLUSIONS: Photorefractive keratectomy is a safe and effective technique for treatment of patients with LASIK flap complications.

Textural interface opacity after descemet stripping automated endothelial keratoplasty: a report of 30 cases and possible etiology.

PURPOSE: Descemet stripping automated endothelial keratoplasty (DSAEK) has its own set of complications including interface abnormalities. This case series presents the largest number of patients who developed textural interface opacity (TIO) at the graft-host interface after DSAEK. METHODS: This is a retrospective multicenter case series of 30 patients from 7 institutions with the finding of TIO. Clinical information collected included donor preparation details, recipient information, and surgical technique. Clinical outcomes included best-corrected visual acuity and status of TIO appearance at the last follow-up visit. Slit-lamp photographs were analyzed and compared. RESULTS: The majority of the patients (73%) had a best-corrected visual acuity of 20/40 or better. Four of the donor tissues were prepared with a microkeratome blade with the same lot number. Six patients had a central interface space between host and donor stromal surfaces--presumed interface fluid but potentially viscoelastic. A slight majority (57%) of patients had improvement in the severity of TIO, with 20% noted to have a complete resolution of TIO (mean follow-up of 11.9 months). Two clinical types of TIO were seen: an elongated type and a punctate type. CONCLUSIONS: Most patients with TIO after DSAEK obtain good visual outcomes. TIO spontaneously improves or even resolves during follow-up without intervention. The etiology of this condition is unknown, but we propose 2 different mechanisms. The elongated type could be secondary to an irregular cut of the donor with the microkeratome blade. The punctate type may be secondary to retained viscoelastic.

Penetrating keratoplasty in active Acanthamoeba keratitis.

PURPOSE: To report the results of penetrating keratoplasty (PK) in active Acanthamoeba keratitis (AK). METHODS: Nine patients with deep stromal infiltrates because of AK were treated with intensive antiamoebic medical therapy followed by PK during the acute infectious phase because of poor clinical response or poor compliance. Antiamoebic therapy was tapered after PK. RESULTS: Visual acuity ranged from 20/15 to 20/50 after an average of 17 months after PK with no signs of recurrences. Patients had rapid resolution of symptoms. CONCLUSION: PK is a viable option for active AK not responding to maximum medical treatment.

Spontaneous reattachment of Descemet stripping automated endothelial keratoplasty lenticles: a case series of 12 patients.

PURPOSE: To review 12 cases of postoperative detachment and spontaneous reattachment of Descemet stripping automated endothelial keratoplasty (DSAEK) lenticles. DESIGN: Retrospective, observational case series. METHODS: This was a review of patients undergoing DSAEK at 7 institutions. Patients who had a significant detachment of their DSAEK lenticle during the postoperative period were identified and divided into 2 groups. Significant detachment was defined as either complete central interface fluid with bare peripheral attachment (group 1) or a free-floating lenticle in the anterior chamber (group 2). Patients who subsequently had a spontaneous reattachment of the lenticle were identified, with data regarding surgical technique and intraoperative and postoperative complications collected for analysis. RESULTS: Our cohort consisted of 12 eyes of 12 patients who met the definition of significant postoperative detachment with subsequent spontaneous reattachment. Four patients had complete central detachment with peripheral attachment (group 1), whereas 8 patients had a free-floating lenticle (group 2). Ten of the 12 patients had a successful outcome as defined as an attached and clear DSAEK lenticle. In our study, reattachment was seen as early as 5 days and as late as 7 months after surgery, with reattachment in 9 of 12 patients by day 25. CONCLUSIONS: Spontaneous reattachment of detached DSAEK lenticles may occur during the postoperative period. The decision of when to bring the patient back for a rebubble ultimately must be made on a case-by-case basis.