Nanohydroxyapatite Coating Attenuates Fibrotic and Immune Responses to Promote Keratoprosthesis Biointegration in Advanced Ocular Surface Disorders.

Keratoprosthesis (KPro) implantation is frequently the only recourse for patients with severe corneal disease. However, problems arise due to inadequate biointegration of the KPro, particularly the PMMA optical cylinder, such as tissue detachment, tissue melting, or eye-threatening infection in the interface. Here, using the AuroKPro as a model prosthesis, a surface functionalization approach─coating the optical cylinder with nanohydroxyapatite (nHAp)─was trialed in rabbit eyes with and without a proceeding chemical injury. In chemically injured eyes, which simulated total limbal epithelial stem cell deficiency, clear benefits were conferred by the coating. The total modified Hackett-McDonald score and area of tissue apposition differences 12 weeks after implantation were 5.0 and 22.5%, respectively. Mechanical push-in tests revealed that 31.8% greater work was required to detach the tissues. These differences were less marked in uninjured eyes, which showed total score and tissue apposition differences of 2.5 and 11.5%, respectively, and a work difference of 23.5%. The improved biointegration could be contributed by the attenuated expression of fibronectin (p = 0.036), collagen 3A1 (p = 0.033), and α-smooth muscle actin (p = 0.045)─proteins typically upregulated during nonadherent fibrous capsule envelopment of bioinert material─adjacent to the optical cylinders. The coating also appeared to induce a less immunogenic milieu in the ocular surface tissue, evidenced by the markedly lower expression of tear proteins associated with immune and stimulus responses. Collectively, the level of these tear proteins in eyes with coated prostheses was 1.1 ± 13.0% of naïve eyes: substantially lower than with noncoated KPros (246.5 ± 79.3% of naïve, p = 0.038). Together, our results indicated that nHAp coating may reduce the risk of prosthesis failure in severely injured eyes, which are representative of the cohort of KPro patients.

Meibomian Gland Dysfunction and Dropout in Diabetic Patients with Non-Proliferative Diabetic Retinopathy.

This study aims to compare meibomian gland (MG) dropout and MG dysfunction (MGD) between patients with diabetes mellitus (DM) with moderate-severe non-proliferative diabetic retinopathy (NPDR) and patients with no diabetes (NDM). This prospective, transversal, age, and gender-matched case-control study included 98 DM and 106 NDM eyes. Dry eye disease (DED) and MGD evaluations were performed, including meibography (Keratograph 5M®). The objective MG dropout percentage was obtained by analyzing meibography images with ImageJ software (v. 1.52o, National Institutes of Health, Bethesda, MD, USA) and was subsequently graded with Arita's meiboscore. The DM duration was 18 ± 9 years. The mean meiboscore (3.8 ± 0.8 vs. 3.4 ± 1.0, p = 0.001), meiboscore severity (p = 0.016), and MG dropout (45.1 ± 0.1% vs. 39.0 ± 0.4%, p < 0.001) were greater in DM than in NDM. All patients showed MG dropout (meiboscore > 1). Lower eyelids showed greater MG dropout in both groups. A correlation with age (r = 0.178, p = 0.014) and no correlations with DM duration or gender (p > 0.005) were observed. Patients with diabetes showed greater corneal staining (1.7 ± 1.3 vs. 0.9 ± 1.1; p < 0.001), reduced corneal sensitivity (5.4 ± 1.1 vs. 5.9 ± 0.4; p < 0.001), lower MG expressibility (3. 9 ± 1.6 vs. 4.4 ± 2.1; p = 0.017), and worse meibum quality (1.9 ± 0.8 vs. 1.7 ± 0.5; p = 0.019). Tear breakup time, osmolarity, MMP-9, Schirmer, and the Ocular Surface Disease Index showed no significant differences. In conclusion, patients with DM with NPDR have greater MG dropout and meiboscore, as well as more severe MGD and DED parameters than persons with NDM.

Femtosecond laser applications in corneal surgery.

Femtosecond laser (FSL) applications in corneal surgery have increased since its inception. Corneal surgery has undergone a tremendous transformation thanks to the introduction of FSL technology. This laser makes precise, three-dimensional incisions while causing minimal damage to surrounding tissue. This review updates and summarizes current and upcoming FSL applications in corneal surgery, current commercially available FSL, and its respective applications. Refractive surgery applications include laser in-situ keratomileusis flaps, refractive corneal lenticule extraction such as small incision lenticule extraction, astigmatic keratotomy, intracorneal ring segments tunnels for keratoconus including corneal allogenic intrastromal ring segments, and presbyopia treatments with intrastromal pockets for corneal inlays and intrastromal incisions (INTRACOR). Keratoplasty applications include penetrating keratoplasty trephination; superficial and deep anterior lamellar keratoplasty trephination, lamellar dissection, and tunnel creation; posterior lamellar keratoplasty donor and recipient preparation; Bowman layer transplantation donor, and recipient preparation; and stromal keratophakia. Other applications include conjunctival graft preparation in pterygium surgery, and keratopigmentation (corneal tattooing). FSL is a surgical instrument widely used in corneal surgery because it improves reproducibility and safety in many procedures.

Face Mask and Tear Film Stability: A Pilot Study of the Objective Measurement of Tear Break-Up Time.

(1) Background: Mask-associated dry eye (MADE) has been associated with increased dry eye symptoms, apparently due to reduced tear break-up time (TBUT). This study aimed to determine the short-term impact of surgical face mask (FM) on tear film stability by measuring non-invasive tear break-up time (NIBUT). (2) Methods: Twenty-six healthy participants had NIBUT evaluated without FM, with surgical FM and with a surgical FM secured to the skin with adhesive tape (TFM). NIBUT-first was measured with Keratograph 5M (K5M, Oculus, Wetzlar, Germany). Each participant had NIBUT measured in four sessions on four consecutive days. Session 1: without FM vs. with FM. Session 2: with FM vs. without FM. Session 3: without FM vs. with TFM. Session 4: with TFM vs. without FM (3). The time between each measured setting was 2 min. Results: The mean ± SD NIBUT without FM was 8.9 ± 3.7, with FM 10.2 ± 4.1, and with TFM 8.4 ± 3.8 s. No significant differences were observed in NIBUT in any of the evaluated settings: without FM vs. with FM (p = 0.247), without FM vs. with TFM (p = 0.915), and with FM vs. with TFM (p = 0.11). (4) Conclusions: This study did not find a significant short-term effect of FM on NIBUT. Other variables or longer periods of exposure might trigger the symptoms and ocular surface alterations in MADE.

Reduced corneal endothelial cell density after toxic anterior segment syndrome (TASS) caused by inadvertent intraocular ointment migration: A case report.

INTRODUCTION AND IMPORTANCE: Toxic anterior segment syndrome (TASS) is an acute sterile inflammation of the anterior segment which may occur after surgery. This case presents endothelial cell density (ECD) loss due to months of TASS caused by intraocular migration of ocular ointment. The chronicity of this case and the clinical consequences are rare in the literature. CASE PRESENTATION: A Colombian 71-year-old man developed TASS secondary to intraocular ointment migration after uneventful cataract surgery with phacoemulsification and intraocular lens placement in the capsular bag. The main complaint for the patient was a chronic red eye, no pain or visual disturbance were reported, rheumatologic diseases were discarded. It was documented the presence of intraocular ointment in the anterior chamber, over the iris and in the anterior chamber angle. The ECD was reduced secondary to TASS and the long-term presence of ointment moving in the anterior chamber, so it had to be removed. CLINICAL DISCUSSION: It is important to avoid using ocular ointment after intraocular surgeries to avoid the risk of ointment migration into the anterior chamber. Intraocular ointments should be removed promptly to reduce ECD loss as documented in the present case report in which after ointment elimination ECD remains stable for 7 years. CONCLUSION: Topical ointments should not be used after routine cataract surgery because of the risk of intraocular ointment migration and subsequent risk of developing TASS and reduced ECD.

Femtosecond laser-assisted corneal transplantation with a low-energy, liquid-interface system.

Femtosecond laser-assisted keratoplasty has been proposed as a treatment option for corneal transplantation. In this study, we investigated and compared the outcomes of Ziemer Z8 femtosecond laser (FSL)-assisted penetrating keratoplasty (PK) using a liquid interface versus flat interface. Thirty fresh porcine eyes underwent FSL-assisted PK with the Z8 using different levels of energies (30%, 90% or 150%) and different interfaces (liquid or flat). The real-time intraocular pressure (IOP) changes, incision geometry, corneal endothelial damage, as well as the accuracy of laser cutting and tissue reaction, were performed and compared. We found that the overall average IOP at all laser trephination stages was significantly higher with the flat interface, regardless of the energy used (68.9 ± 15.0 mmHg versus 46.1 ± 16.6 mmHg; P < 0.001). The overall mean laser-cut angle was 86.2º ± 6.5º and 88.2º ± 1.0º, for the liquid and flat platform respectively, indicating minimal deviation from the programmed angle of 90º. When high energy (150%) was used, the endothelial denuded area was significantly greater with the flat interface than with liquid interface (386.1 ± 53.6 mm2 versus 139.0 ± 10.4 mm2 P = 0.02). The FSL cutting did not cause obvious tissue reaction alongside the laser cut on histological evaluation. The results indicated a liquid interface is the preferable choice in FSL-assisted corneal transplantation.

A Novel Approach of Harvesting Viable Single Cells from Donor Corneal Endothelium for Cell-Injection Therapy.

Donor corneas with low endothelial cell densities (ECD) are deemed unsuitable for corneal endothelial transplantation. This study evaluated a two-step incubation and dissociation harvesting approach to isolate single corneal endothelial cells (CECs) from donor corneas for corneal endothelial cell-injection (CE-CI) therapy. To isolate CECs directly from donor corneas, optimization studies were performed where donor Descemet's membrane/corneal endothelium (DM/CE) were peeled and incubated in either M4-F99 or M5-Endo media before enzymatic digestion. Morphometric analyses were performed on the isolated single cells. The functional capacities of these cells, isolated using the optimized simple non-cultured endothelial cells (SNEC) harvesting technique, for CE-CI therapy were investigated using a rabbit bullous keratopathy model. The two control groups were the positive controls, where rabbits received cultured CECs, and the negative controls, where rabbits received no CECs. Whilst it took longer for CECs to dislodge as single cells following donor DM/CE incubation in M5-Endo medium, CECs harvested were morphologically more homogenous and smaller compared to CECs obtained from DM/CE incubated in M4-F99 medium (p < 0.05). M5-Endo medium was hence selected as the DM/CE incubation medium prior to enzymatic digestion to harvest CECs for the in vivo cell-injection studies. Following SNEC injection, mean central corneal thickness (CCT) of rabbits increased to 802.9 ± 147.8 µm on day 1, gradually thinned, and remained clear with a CCT of 385.5 ± 38.6 µm at week 3. Recovery of corneas was comparable to rabbits receiving cultured CE-CI (p = 0.40, p = 0.17, and p = 0.08 at weeks 1, 2, and 3, respectively). Corneas that did not receive any cells remained significantly thicker compared to both SNEC injection and cultured CE-CI groups (p < 0.05). This study concluded that direct harvesting of single CECs from donor corneas for SNEC injection allows the utilization of donor corneas unsuitable for conventional endothelial transplantation.

Resolution of giant ocular surface squamous neoplasia with topical 5-fuorouracil 1.

An 82-year-old man presented with a left eye elevated single ocular surface squamous neoplasia. The tumor involved 360° of limbus, three quadrants of cornea and conjunctiva; this was compatible with the diagnosis of giant ocular surface squamous neoplasia. Topical 5-fluorouracil 1% was planned four times daily for 1 week followed by 3 weeks off-treatment. Patient inadvertently continued 5-fluorouracil, four times daily for 4 weeks, presenting with clinical resolution of the ocular surface squamous neoplasia and subtotal corneal epithelial defect associated with 5-fluorouracil toxicity. One month later, we observed a transparent cornea and no signs of toxicity. Total tumor resolution was observed for at least 6 months of follow-up.