Newer approaches to dry eye therapy: Nanotechnology, regenerative medicine, and tissue engineering.

Definitive treatment of dry eye disease (DED), one of the commonest ocular surface disorders, has remained elusive despite several recent advances in better diagnostics and the introduction of newer therapeutic molecules. The current treatment paradigms rely heavily on lubricating eye drops and anti-inflammatory agents that may need to be used long-term and are mainly palliative. Research is ongoing not only for a curative treatment option but also to improve the potency and efficacy of existing drug molecules through better formulations and delivery platforms. In the past two decades, significant advancement has been made in terms of preservative-free formulations, biomaterials such as nanosystems and hydrogels, stem cell therapy, and creation of a bioengineered lacrimal gland. This review comprehensively summarizes the newer approaches to DED treatment, which are biomaterials such as nanosystems, hydrogels, and contact lenses for drug delivery, cell and tissue-based regenerative therapy for damaged lacrimal gland and ocular surface, and tissue engineering for developing artificial lacrimal gland. Also, their potential efficacies in animal models or in vitro studies and possible limitations are discussed. The ongoing research looks promising and needs to be supported with clinical efficacy and safety studies for human use.

Relationship of Density, Depth, and Surface Irregularity of Superficial Corneal Opacification with Visual Acuity.

PURPOSE: To explore the relationship between the density, depth, and surface irregularity of superficial corneal opacities and vision. METHODS: This prospective imaging study included 19 patients with unilateral superficial corneal opacification due to scarring post-microbial keratitis. Each eye underwent an assessment of uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), contact lens corrected visual acuity (CLCVA), and Scheimpflug and anterior segment optical tomography imaging. Regression analysis was performed to detect the association between density, depth of scarring, and the surface irregularity in terms of higher order aberrations (HOA), and keratometry and UCVA, CLCVA, and the difference between BSCVA and CLCVA. RESULTS: The mean logMAR UCVA, BSCVA, and CLCVA were 0.76, 0.35, and 0.28, respectively. The corneal scars had a mean thickness of 158.7 ± 61 µ and density of 65.73 ± 24.46 GSU. Bivariate analysis model for UCVA showed an association with Z42 secondary astigmatism (p = 0.02), Z44 quadrafoil (p = 0.01), combined coma Z3 ± 1(p = 0.03), and combined HOA Z3-Z6 (p = 0.045), out of which Z44 Quadrafoil (p = 0.04) was most significant with multivariate analysis. Bivariate analysis for BCVA-CLVA showed association with Z31 coma horizontal (p = 0.04), Z33 oblique trefoil (p = 0.02), Z40 primary spherical aberration (p = 0.008), and Z5 - 5 (p = 0.007), out of which Z31 horizontal coma (p = 0.04) and Z40 spherical aberration (p = 0.009) were significant on multivariate analysis. Change in densitometry, corneal thickness, epithelial:stromal reflectivity ratio, scar depth, and keratometry did not show any significant association with UCVA, BSCVA-CLCVA, or CLCVA. CONCLUSION: In superficial corneal stromal scarring, deranged surface irregularity parameters like higher-order aberrations affect the final visual acuity more than the depth or density of the opacity.

Descemet Membrane Endothelial Keratoplasty and Goniosynechialysis in Iridocorneal Endothelial Syndrome: Surgical Perspective and Long-Term Outcomes.

PURPOSE: The purpose of this study was to report the long-term outcomes of Descemet membrane endothelial keratoplasty (DMEK) with goniosynechialysis in eyes with iridocorneal endothelial syndrome with an emphasis on the surgical technique. METHODS: This was a retrospective series of 5 eyes of 5 patients undergoing a DMEK procedure at a tertiary eye care institute by a single surgeon. Modifications in the standard surgical technique, including the release of peripheral anterior synechiae, peripheral descemetorhexis, the release of adherent membranes, maneuvers in the anterior chamber with or without cataract extraction were logged. Long-term outcomes of the surgery in these patients are reported. RESULTS: Five DMEK procedures were performed in 5 eyes of 5 patients. The average age of the patients was 48.2 ± 10.8 years, and the donor was 55.2 ± 3.2 years with a mean endothelial cell density (ECD) of 2784.6 ± 231 cells/mm 2 . After a mean follow-up period of 29.6 months (24-41 mo), all the 5 grafts remained clear; the mean BCVA at the last follow-up was 0.18 ± 0.17 logarithm of the minimum angle of resolution with a mean ECD of 1086.2 ± 338 cells/mm 2 with a 61.1% reduction in ECD. intra ocular pressure was normal in all the cases. None of the patients had graft detachments that required rebubbling, and all eyes had a clear graft at the last follow-up. CONCLUSIONS: DMEK can be performed successfully in a case with iridocorneal endothelial syndrome with good visual outcomes with modifications to the surgical technique, including peripheral anterior synechiae release and minimizing surgical manipulation.

Anterior segment imaging using a simple universal smartphone attachment for patients.

To assess the utility of a universal smartphone attachment to capture images of the anterior segment of the eye, we conducted a retrospective analysis of 344 images captured using a smartphone by the patients to identify factors affecting image quality, such as lack of perspective, lack of focus, improper illumination, and resolution. Based on this analysis, a universal smartphone attachment named GrabiTMLite and a protocol for anterior segment imaging were designed and validated in the first prospective arm of 60 patients. These images were then compared with the same eyes imaged on the gold standard slit-lamp photography. In the second prospective arm, nine patients were trained to use the GrabiTM Lite with the imaging protocol, and the images were assessed for utility in arriving at a diagnosis. A total of 178 images were analyzed using a questionnaire by masked observers. The images were evaluated based on their quality and suitability in clinical decision-making, risk stratification for triage for referral to a tertiary eye care centre. The quality of 344 images captured by patients using only their smartphone was rated as good 24 (7%), average 209 (60.8%), and poor in 111 (32.2%). Of these, 55 (16%) images were deemed suitable for clinical decision-making, and 224 (65.6%) images were adequate for risk stratification. Lack of perspective, focus, illumination, and resolution were seen in 167 (51.2%), 284 (87.1%), 226 (69.3%), and 126 (38.7%) images, respectively. These metrics improved in the next iteration of 178 images captured by patients using Grabi Lite + imaging protocol to good 103 (57%), average 58 (32.6%), and bad 17 (19.6%) (p < .001 using chi-square test). Images deemed suitable for clinical decision-making, and risk stratification for triage also improved to 80 (45%), 158 (88.8%) (p < .001 using chi-square test), respectively. Adherence to protocol was seen in 98 (55.5%) images, of which all were suitable for risk stratification, while of these images, 66 (67.3%) were eligible for clinical decision making. In comparison with slit-lamp photography, out of 120 responses by masked observers to images captured by GrabiTM Lite with the imaging protocol, 63 (52.85%) were suitable for clinical decision-making, and 68 (57%) were graded to be between 70 and 99% of the quality of the slit lamp photographs. The GrabiTM lite with imaging protocol training is an effective tool to improve anterior segment imaging, potentially allowing smartphone use for teleconsultations. This device may serve as a universal solution for all smartphones with the patient as the user and is of value in the future of tele-ophthalmology.

Corneal oedema with in situ implantable collamer lens: a challenging scenario for descemet membrane endothelial keratoplasty.

A 27-year-old woman had foggy vision and photophobia since 10 months after implantation of implantable collamer lens (ICL STAAR Surgical AG, Nidau, Switzerland) with evidence of corneal decompensation and no cataract formation. Descemet membrane endothelial keratoplasty in phakic eyes is challenging, considering presence of posterior chamber phakic intraocular lens (IOL), decreasing the space available in anterior chamber to manoeuvre the graft. Need of inferior peripheral iridotomy in presence of central hole technology in ICL depends on the dynamics of full chamber air bubble. At 8 months, vision had improved to 20/20 and normal IOP with well-attached graft, stable phakic IOL and clear lens.

A reliable animal model of corneal stromal opacity: Development and validation using in vivo imaging.

PURPOSE: To validate an animal model of corneal stromal opacity by using objective vision-independent in vivo imaging metrics. METHODS: This was a prospective study, with two arms: (i) observational human arm which included 14 patients with healed unilateral ulcerative keratitis; and (ii) experimental rabbit arm, which included 6 New Zealand white rabbits. A 3-mm central wound was created in the left eye of the rabbits by manually removing 200-250 µm of the superficial stroma, followed by rotating-burr application. Both groups underwent photography, high-resolution anterior segment optical coherence tomography, and Scheimpflug imaging using similar diagnostic platforms and standardized image capturing protocols. Parameters studied were relative change in (i) corneal thickness; (ii) corneal epithelial: stromal (E:S) reflectivity ratio; (iii) corneal stromal light scattering using densitometry; and (iv) central corneal keratometry. RESULTS: In the experimental arm, there was a significant decrease in corneal thickness (273 ± 51.3 vs. 407.3 ± 10.3 µm, p = 0.0038), E:S reflectivity ratio (0.71 ± 0.09 vs. 0.99 ± 0.06, p = 0.0018), and keratometry (40.4 ± 2.3 vs. 45.8 ± 0.9D, p = 0.0033) and increase in densitometry (54.2 ± 11.65 vs.18.7 ± 3.8 GSU, p = 0.0001) from baseline, which stabilized at 4 to 8-weeks post-wounding (p > 0.3632). At 8-weeks, the relative change from baseline in corneal thickness (28.4 ± 13.5% vs.22.4 ± 13%, p = 0.368), E:S reflectivity ratio (28.1 ± 11.5% vs. 30.6 ± 8.9%, p = 0.603), corneal densitometry (204.17 ± 97.3% vs. 304.9 ± 113.6%, p = 0.1113), and central corneal keratometry (13.6 ± 6.9% vs. 18.9 ± 7.4%, p = 0.1738) in rabbits was similar to human corneal scars. CONCLUSION: The animal model of corneal opacification was objectively comparable to human post-keratitis scars and can be valuable for in vivo evaluation of emerging therapies for corneal opacities.