The Value of Eccentric Infrared Photorefraction in Evaluating Keratoconus.

SIGNIFICANCE: Nonlinearity in the luminance profile of eccentric, infrared photorefraction may be used to differentiate corneal diseases such as keratoconus that distort the cornea, relative to regular refractive errors. PURPOSE: This study aimed to determine the profile of eccentric, infrared photorefraction in keratoconus as a prototypical disease model for distorted corneas and identify a parameter in this profile for differentiating such disease conditions from healthy controls. METHODS: Photorefraction reflex of 75 eyes with forme fruste to advanced keratoconic cases and that of 75 eyes of controls with regular refractive errors (spherical equivalent, +0.50 to -11.75 D; astigmatism, -0.50 to -4.50 D across 0 to 180° axes) were obtained over their natural pupils under unaided viewing using a custom-designed photorefractor placed at 1 m from the subject. The test was repeated in 10 controls with 4 and 6 D of trial-lens-induced myopia and myopic astigmatism at 0, 90, 45, and 135°. Linear regression was performed on the luminance profile across the pupil, and the departure of the data from linearity was estimated using the average residual error of the fit (Res avg ). RESULTS: Photorefraction profiles varied linearly across the pupil in controls, with slopes increasing with refractive error ( r = 0.87; P < .001) and Res avg remaining invariant of refractive error ( r = -0.29; P > .4). Corresponding profiles in keratoconus significantly departed from linearity, with Res avg progressively increasing with disease severity ( r = 0.66; P < .001). Res avg of 0.03 gray-scale units/pixel distinguished keratoconus from controls with sensitivity increasing from 66.7 to 100% for mild to advanced keratoconus and specificity remaining ≥97.1% across disease severity. Induced myopia and myopic astigmatism produced predictable changes in luminance profile slopes but with no change in Res avg values. CONCLUSIONS: Unlike regular myopia and astigmatism, the photorefraction reflex is significantly nonlinear in keratoconus because of the distorted cornea. Measures of nonlinearity in luminance profile may be incorporated in commercial photorefractors for differentiating such disease conditions from regular refractive errors.

Visual photosensitivity threshold and objective photosensitivity luminance in healthy human eyes assessed using an automated ocular photosensitivity analyser: a step towards translation of a clinical tool for assessing photophobia.

PURPOSE: To evaluate the visual photosensitivity threshold and objective photosensitivity luminance in healthy eyes, thereby providing a normative dataset that will lead to a better understanding of diseases causing photophobia. METHODS: This was a prospective cross-sectional study. Emmetropes whose visual acuity was better than 0.18 logMAR (6/9) with no other ocular abnormality were included. Headache Impact Test-6 and visual light sensitivity questionnaires were administered. Visual photosensitivity threshold was measured subjectively using the ocular photosensitivity analyser. Objective photosensitivity luminance was assessed manually by evaluating videos recorded using an infrared camera and noting the intensity of light at the first squeezing reflex. RESULTS: Seventy five normal subjects (age range, 7-71 years) were included. Median age was 32.7 years (inter-quartile range, 20.3-47.9 years). Forty (53.3%) were males. Median Headache Impact Test score was 38 (inter-quartile range, 36-42) and visual light sensitivity questionnaire score was 11 (inter-quartile range, 8-15). Mean (standard deviation) right eye, left eye and binocular visual photosensitivity threshold was 3.34 (0.78), 3.33 (0.81) and 3.37 (0.78) loglux, respectively. There was a significant negative correlation of visual light sensitivity questionnaire scores with right eye, left eye and binocular visual photosensitivity thresholds, and positive correlation of age with binocular visual photosensitivity thresholds. Mean (standard deviation) right eye, left eye and binocular objective photosensitivity luminance was 3.25 (0.55), 3.35 (0.47) and 3.15 (0.52) loglux, respectively. Age was only positively correlated with binocular objective photosensitivity luminance, and there was no correlation between age and right eye or left eye objective photosensitivity luminance. CONCLUSIONS: The study characterised, for the first time, objective photosensitivity luminance and established normative data for both visual photosensitivity threshold and objective photosensitivity luminance. The data will help in understanding the pathophysiology of diseases causing photophobia, monitoring the disease progression and evaluating treatment modalities.

Complications and visual outcomes of cataract surgery in patients with pseudoexfoliation.

PURPOSE: To compare outcomes of cataract surgery performed by ophthalmic trainees and consultants in patients associated with pseudoexfoliation (PXF) METHODS: Retrospective review of medical records of all patients with PXF who had undergone cataract surgery from January 2016 to December 2018 at L V Prasad Eye Institute, Hyderabad, India, were analysed RESULTS: A total of 914 eyes were included in the study; surgeries on 501 (54.8%) eyes with PXF were performed by trainees, while 413 (45.2%) were performed by consultants. Posterior capsule rupture (PCR) with vitreous loss (VL) occurred in significantly fewer eyes operated on by consultants (n = 8, 1.9%) than those operated on by trainees (n = 23, 4.5%) (p = 0.002). Eyes that underwent small incision cataract surgery (n = 100, 21.2%) had a significantly greater number of complications than those that underwent phacoemulsification (n = 31, 7.1%) (p = 0.00001). Multivariate logistic regression analysis shows that chances of a complication are higher when operated on by a trainee (OR = 1.59, 95% CI: 1.09-2.34, p = 0.02).The mean logMAR corrected distance visual acuity of patients one month post-surgery was significantly higher for patients in the consultant group (0.15 ± 0.3) than for those in the trainee group (0.2 ± 0.4) (p = 0.003). CONCLUSION: Patients with PXF operated on by trainees for cataract had a relatively higher risk of developing PCR with VL and had poorer visual outcomes than those operated on by consultants.

Longitudinal Changes in Optical Quality, Spatial Vision, and Depth Vision after Laser Refractive Surgery for Myopia.

SIGNIFICANCE: Laser refractive surgery procedures are efficacious at correcting myopia, but they result in long-term deterioration of optical quality that affects monocular and binocular visual performance. The study shows that the optical quality of the two eyes needs to be similar to optimize binocular visual performance after surgery. PURPOSE: This study aimed to systematically analyze longitudinal changes in optical quality, high- and low-contrast logMAR acuity and random-dot stereoacuity before and after three refractive surgery procedures for correcting myopia. METHODS: A total of 106 subjects (laser-assisted in situ keratomileusis, 40; photorefractive keratectomy, 26; small-incision lenticule extraction, 40) with myopia and astigmatism ≤1.5 D participated in this prospective cohort-based study. All aforementioned outcome variables were measured in both eyes pre-operatively and 1 week and 1, 3, and 6 months post-operatively. RESULTS: Pre-operative myopic spherical equivalent of refraction (median [25th to 75th interquartile range], -6.4 D [-8.0 to -4.2 D] for laser-assisted in situ keratomileusis, -4.3 D [-5.0 to -3.5 D] for photorefractive keratectomy, -5.5 D [-6.5 to -4.3 D] for small-incision lenticule extraction) was corrected to within ±0.75 D of emmetropia in all cohorts up to 6 months post-operatively (P < .001). Higher-order wavefront aberrations, uncorrected high- and low-contrast logMAR acuity, and stereoacuity all worsened and remained so up to 6 months post-operatively, relative to pre-operative values (P < .001). Stereoacuity worsened with both interocular average and difference in the magnitude of higher-order aberrations, whereas logMAR acuities worsened only with interocular average of these aberrations (r ≥ 0.40; P < .01 for all). CONCLUSIONS: Although the refractive surgery procedures tested here correct myopia, they result in a sustained (up to 6 months) loss of optical quality and spatial and depth-related visual functions post-operatively. Both interocular average and difference in the eye's optical quality seem to impair binocular visual functions after refractive surgery for myopia.

Treatment Practices and Outcomes of Meibomian Gland Dysfunction at a Tertiary Center in Southern India.

OBJECTIVE: To describe the current treatment practices for meibomian gland dysfunction (MGD) at a tertiary eye center, together with the subjective outcomes and compliance behaviors of patients. METHODS: This retrospective cohort study reviewed medical records for MGD severity grading, treatment prescribed, and follow-up schedule. In addition, participants were surveyed to gauge subjective outcomes and treatment adherence. RESULTS: Eight hundred ten patients were diagnosed with "MGD" or "meibomitis" and had a total of 14 different treatment combinations prescribed. In 3.0% of cases, there was no treatment specified. As MGD severity increased, it became more likely that management would be applied and this was also associated with significantly longer treatment durations (P=0.02) and shorter follow-up periods (P<0.001). Posttreatment subjective outcomes and treatment adherence surveys had a response rate of 36.7% and 24.1% respectively. Overall, 53.5% reported sustained improvement, 40.7% no improvement, and 5.7% experienced temporary relief. Although no treatment regimen seemed to be more efficacious than others, patients showed greater adherence when using topical reagents compared with lid hygiene measures (P≤0.002). CONCLUSION: Clinicians, in this large tertiary eye center, use a wide range of treatment regimens to manage MGD. This suggests the need for development of standard management protocols. Whether alone, or in combination, no MGD treatment significantly improved subjective symptoms, a result that may be influenced by compliance behaviors. Use of topical reagents (eye drops or ointment) seemed to be associated with the best compliance. Future focus on more effective MGD treatments is needed to improve practical outcomes.

The use of Bowman's layer vertical topographic thickness map in the diagnosis of keratoconus.

PURPOSE: To evaluate the use of Bowman's layer (BL) vertical topographic thickness maps in diagnosing keratoconus (KC). DESIGN: Prospective, case control, interventional case series. PARTICIPANTS: A total of 42 eyes: 22 eyes of 15 normal subjects and 20 eyes of 15 patients with KC. INTERVENTION: Bowman's layer 2-dimensional 9-mm vertical topographic thickness maps were created using custom-made ultra high-resolution optical coherence tomography. MAIN OUTCOME MEASURES: Bowman's layer average and minimum thicknesses of the inferior half of the cornea, Bowman's ectasia index (BEI; defined as BL minimum thickness of the inferior half of the cornea divided by BL average thickness of the superior half of the cornea multiplied by 100), BEI-Max (defined as BL minimum thickness of the inferior half of the cornea divided by BL maximum thickness of the superior half of the cornea multiplied by 100), keratometric astigmatism (Ast-K) of patients with KC, and average keratometric (Avg-K) readings. RESULTS: In patients with KC, BL vertical thickness maps disclosed localized relative inferior thinning of the BL. Inferior BL average thickness (normal = 15±2, KC = 12±3 µm), inferior BL minimum thickness (normal = 13±2, KC = 7±3 µm), BEI (normal = 91±7, KC = 48±14), and BEI-Max (normal = 75±8; KC = 40±13) all showed highly significant differences in KC compared with normal subjects (P< 0.001). Receiver operating characteristic (ROC) curve analysis showed excellent predictive accuracy for BEI and BEI-Max with 100% sensitivity and specificity (area under the curve [AUC] of 1) with cutoff values of 80 and 60, respectively. The AUC of inferior BL average thickness and minimum thickness were 0.87 and 0.96 with a sensitivity of 80% and 93%, respectively, and a specificity of 93% and 93%, respectively. Inferior BL average thickness, inferior BL minimum thickness, BEI, and BEI-Max correlated highly to Ast-K (R = -0.72, -0.82, -0.84, and -0.82, respectively; P< 0.001) and to Avg-K (R = -0.62, P< 0.001; R = -0.59, P = 0.001; R = -0.60, P< 0.001; and R = -0.59, P = 0.001, respectively). CONCLUSIONS: Bowman's layer vertical topographic thickness maps of patients with KC disclose characteristic localized relative inferior thinning. Inferior BL average thickness, inferior BL minimum thickness, BEI, and BEI-Max are qualitative and quantitative indices for the diagnosis of KC that accurately correlate with the severity of KC. In our pilot study, BEI and BEI-Max showed excellent accuracy, sensitivity, and specificity in the diagnosis of KC.

Central Toxic Keratopathy After Collagen Cross-Linking: A Case Series.

PURPOSE: The aim of this study was to report a case series of central toxic keratopathy (CTK) after collagen cross-linking (CXL) in keratoconus. METHODS: This is a retrospective case series between January 2020 and September 2021. In this period, CXL was performed for progressive keratoconus in 964 eyes. CXL was performed using the epithelium-off accelerated protocol in all patients with a riboflavin soak time of 20 minutes and a UVA light exposure of 9 mW for 10 minutes using the Avedro KXL (Glaukos Inc, Aliso Viejo, CA) cross-linking system. RESULTS: Twelve of 964 eyes (1.2%) developed CTK within 1 week of CXL. All patients presented with well-circumscribed, central disciform haze that was broader in the anterior stroma and narrower in the posterior stroma. We noted initial flattening in keratometry up to 3 months post-CXL in these patients, which gradually steepened over 12 months, but did not reach preoperative levels. We also noted exuberant flattening in pachymetry in the first 3 months, which improved over 12 months. There was a statistically significant decrease in pachymetry in patients who developed CTK at 3 and 12 months postoperatively when compared to patients who underwent CXL but did not develop CTK. CONCLUSIONS: Several reports of CTK postrefractive surgery have been described previously. However, the association of CXL in the development of CTK has not been described previously. Here, we elucidated the clinical features of CTK after CXL and how it differs from corneal scarring or haze that occurs post-CXL.

RiTe conjugate mediated corneal collagen crosslinking, a novel therapeutic intervention for keratoconus - in vitro and in vivo study.

Corneal collagen crosslinking (CXL) is an effective method to halt the disease progression of keratoconus, a progressive corneal dystrophy leading to cone shaped cornea. Despite the efficacy of standard protocol, the concerning step of this procedure is epithelial debridement performed to facilitate the entry of riboflavin drug. Riboflavin, a key molecule in CXL protocol, is a sparsely permeable hydrophilic drug in corneal tissues. The present study has employed cell penetrating peptide (CPP), Tat2, to enhance the penetration of riboflavin molecule, and thereby improve currently followed CXL protocol. This study demonstrates approximately two-fold enhanced uptake of CPP riboflavin conjugate, Tat2riboflavin-5'Phosphate (RiTe conjugate), both in vitro and in vivo. Two different CXL protocols (Epi ON and Epi OFF) have been introduced and implemented in rabbit corneas using RiTe conjugate in the present study. The standard and RiTe conjugate mediated CXL procedures exhibited an equivalent extent of crosslinking in both the methods. Reduced keratocyte loss and no endothelial damage in RiTe conjugate mediated CXL further ascertains the safety of the proposed CXL protocols. Therefore, RiTe conjugate mediated CXL protocols present as potential alternatives to the standard keratoconus treatment in providing equally effective, less invasive and patient compliant treatment modality.

Keratoconus in India: Clinical presentation and demographic distribution based on big data analytics.

PURPOSE: This paper aims to describe the clinical presentation and demographic distribution of keratoconus (KCN) in India by analyzing the electronic medical records (EMR) of patients presenting at a multitier ophthalmology hospital network. METHODS: This cross-sectional hospital-based study included the data of 2,384,523 patients presenting between January 2012 and March 2020. Data were collected from an EMR system. Patients with a clinical diagnosis of KCN in at least one eye were included in this study. Univariate analysis was performed to identify the prevalence of KCN. A multiple logistic regression analysis was performed using R software (version 3.5.1), and the odds ratios are reported. RESULTS: Data were obtained for 14,749 (0.62%) patients with 27,703 eyes diagnosed with KCN and used for the analysis. The median age of the patients was 22 (inter-quartile range (IQR): 17-27). In total, 76.64% of adults (odds ratio = 8.77; P = <0.001) were affected the most. The majority of patients were male (61.25%), and bilateral (87.83%) affliction was the most common presentation. A significant proportion of the patients were students (63.98%). Most eyes had mild or no visual impairment (<20/70; 61.42%). Corneal signs included ectasia (41.35%), Fleischer ring (44.52%), prominent corneal nerves (45.75%), corneal scarring (13.60%), Vogts striae (18.97%), and hydrops (0.71%). Only 7.85% showed an association with allergic conjunctivitis. A contact lens clinic assessment was administered to 47.87% of patients. Overall, 10.23% of the eyes affected with KCN underwent a surgical procedure. the most common surgery was collagen cross-linking (8.05%), followed by deep anterior lamellar keratoplasty (1.13%) and penetrating keratoplasty (0.88%). CONCLUSION: KCN is usually bilateral and predominantly affects males. It commonly presents in the second and third decade of life, and only a tenth of the affected eyes require surgical treatment.

Corneal thickness in keratoconus: comparing optical, ultrasound, and optical coherence tomography pachymetry.

PURPOSE: To compare the central and peripheral pachymetry measurements determined using Orbscan IIz (Bausch & Lomb, Rochester, NY), Visante optical coherence tomography (OCT; Carl Zeiss Meditec, Dublin, CA), and RTVue OCT (Oculus Technologies, Wynwood, WA) with ultrasound pachymetry in eyes with established keratoconus and to evaluate the agreement between them. DESIGN: Evaluation of diagnostic technologies. PARTICIPANTS: One hundred six eyes of 67 consecutive patients with a clinical diagnosis of keratoconus ranging in age from 12 to 40 years. METHODS: Central corneal thickness (CCT) was determined by all the 4 techniques. Peripheral corneal thicknesses were determined using Orbscan IIz, Visante OCT, and RTVue at 8 points (superior, inferior, temporal, nasal, superior-temporal, inferior-temporal, superior-nasal, and inferior-nasal) all in the 5.0- to 7.0-mm arcuate zone. MAIN OUTCOME MEASURES: Central and peripheral keratoconus thickness. RESULTS: Ultrasound pachymetry determined significantly higher CCT values than Orbscan IIz (P<0.001), Visante (P<0.001), and RTVue (P = 0.037), with a mean ± standard deviation difference of 14±3 µm, 13±2 µm, and 5±3 µm, respectively. The mean CCT difference was minimal (1±3 µm; P = 0.69) between the Orbscan IIz and Visante. A strong correlation was found (r>0.80) between all the CCT measurement techniques. Orbscan IIz significantly overestimated the peripheral thickness compared with the rest, and the mean differences ranged between 21 and 60 µm. Mean peripheral thickness differences between RTVue and Visante OCT always remained less than 20 µm. Weak correlations and larger limits of agreement were found between the techniques in thinner and peripheral zones. CONCLUSIONS: Orbscan IIz, Visante, RTVue, and ultrasound pachymetry show high correlation, although Orbscan IIz and Visante significantly underestimated CCT measurements compared with ultrasound pachymetry in keratoconus. Orbscan IIz significantly overestimated peripheral corneal thickness compared with RTVue and Visante.

Agreement between Pentacam and IOL master in patients undergoing toric IOL implantation.

PURPOSE: To investigate inter-device agreement between the Pentacam (Optikgerate GmbH, Wetzlar, Germany) and IOLMaster (Carl Zeiss Meditec, Jena, Germany) in measuring corneal power, cylinder, and axis of astigmatism. METHODS: Retrospective case series reviewing the status of eyes after toric IOL implantation to evaluate inter-device agreement in measuring corneal power, cylinder, and axis of astigmatism. RESULTS: Forty-nine eyes from 41 patients were evaluated. Agreement for corneal power and cylinder were deemed good and moderate, with 95% limits of agreement of -1.02 to +1.13 and -1.37 to +1.09 diopters (D), respectively. Agreement for axis of astigmatism was only fair, with a mean absolute difference of 8.9 degrees (range: 0.3 to 37.7 degrees, standard deviation: 8.79 degrees). Thirty percent of eyes had a 10-degree or greater difference in axis measurements, and 13% of eyes had a 20-degree or greater difference in measurements. Analysis by multivariate logistic regression showed higher cylinder powers associated with discrepant corneal power measurements (odds ratio: 3.46, P = .02), and increasing age was associated with discrepant axis measurements (odds ratio: 1.09, P = .03). Overall, there was no significant difference in accuracy predicting postoperative spherical equivalent refraction. CONCLUSIONS: Pentacam and IOLMaster agree well for corneal power but less so for cylinder and axis of astigmatism and thus cannot be used interchangeably.

Complications of femtosecond laser-assisted re-treatment for residual refractive errors after LASIK.

PURPOSE: To report complications of femtosecond laser-assisted re-treatment by the creation of side cuts within the old flaps for residual refractive error after primary LASIK in two patients. METHODS: Case report. RESULTS: Three eyes of two patients had complications with a circumferential sliver of stromal tissue displaced during surgery due to overlap of old and new side cuts. The displaced tissue was repositioned and corneal anatomy was restored. Two of three eyes demonstrated improvement in the uncorrected visual acuity, whereas one eye lost two lines of corrected visual acuity due to loss of tissue at side cut resulting from flap manipulation, which was done at 1 week. CONCLUSIONS: These cases demonstrate a complication of femtosecond laser-enabled side-cut for LASIK enhancement and factors that may lead to this complication and precautions to avoid it.

Comparison of IOL power calculation methods and intraoperative wavefront aberrometer in eyes after refractive surgery.

PURPOSE: To compare preoperative methods for calculating intraocular lens (IOL) power versus the intraoperative wavefront aberrometer in eyes with a history of refractive surgery. METHODS: A retrospective study of 46 eyes (33 patients) with previous refractive surgery that underwent subsequent cataract surgery was conducted. Suggested IOL power predicted by ORange intraoperative wavefront aberrometer (WaveTec Vision Systems, Inc., Aliso Viejo, CA) was compared to power predicted by the (1) SRK-T formula using keratometry and axial length measurements from the IOLMaster (Carl Zeiss Meditec, Dublin, CA), (2) average central keratometry (Avg K) from corneal topography, and (3) average IOL power predicted by the American Society of Cataract and Refractive Surgery (ASCRS) web site. No historical information was used for the calculations. IOL power required for emmetropia was back-calculated using manifest refraction and implanted IOL power after cataract surgery. RESULTS: Mean age was 60 ± 7.9 years. Fifteen percent had a history of myopic photorefractive keratectomy (n = 7), 57% myopic LASIK (n = 26), 13% hyperopic LASIK (n = 6), and 22% radial keratectomy (RK) (n = 10). In 37% of cases, ORange predicted IOL power to within ±0.50 diopters (D) of emmetropia, compared to 30% for IOLMaster keratometry, 26% for Avg K, and 17% for ASCRS web site. In eyes after myopic treatment, ORange, IOLMaster, Avg K, and ASCRS web site predicted within ±0.50 D of emmetropia in 39%, 27%, 24%, and 18%, respectively, and within ±1.0 D in 60%, 39%, 39%, and 51%, respectively. In eyes after RK, ORange, Avg K, and ASCRS web site predicted to within ±0.50 D of emmetropia in 14% and the IOLMaster in 43% cases. CONCLUSIONS: Although the ORange most often predicted to within ±0.5 D of emmetropia, no method was able to achieve this accuracy more than 50% of the time. Predictions for eyes after RK were worse than for other types of refractive procedures.

The Evolution of Diagnostics for Keratoconus: From Ophthalmometry to Biomechanics.

PURPOSE: To enumerate the various diagnostic modalities used for keratoconus and their evolution over the past century. METHODS: A comprehensive literature search including articles on diagnosis on keratoconus were searched on PUBMED and summarized in this review. RESULTS: Initially diagnosed in later stages of the disease process through clinical signs and retinoscopy, the initial introduction of corneal topography devices like Placido disc, photokeratoscopy, keratometry and computer-assisted videokeratography helped in the earlier detection of keratoconus. The evolution of corneal tomography, initially with slit scanning devices and later with Scheimpflug imaging, has vastly improved the accuracy and detection of clinical and sub-clinical disease. Analyzing the alteration in corneal biomechanics further contributed to the earlier detection of keratoconus even before the tomographic changes became evident. Anterior segment optical coherence tomography has proven to be a helpful adjuvant in diagnosing keratoconus, especially with epithelial thickness mapping. Confocal microscopy has helped us understand the alterations at a cellular level in keratoconic corneas. CONCLUSION: Thus, the collective contribution of the various investigative modalities have greatly enhanced earlier and accurate detection of keratoconus, thus reducing the disease morbidity.

A goat eye, wet lab model for training in Descemet membrane endothelial keratoplasty.

Here we describe a new, non-human, ex-vivo model (goat eye model) for training surgeons in DMEK surgeons. In a wet lab setting, goat eyes were used to obtain a pseudo-DMEK graft of 8 mm from the goat lens capsule that was injected into another goat eye with the same maneuvers described for human DMEK. The DMEK pseudo-graft can be easily prepared, stained, loaded, injected, and unfolded into the goat eye model reproducing the similar maneuvers used for DMEK in a human eye, except for the descemetorhexis, which cannot be performed. The pseudo-DMEK graft behaves similar to human DMEK graft and useful for surgeons to experience and understand steps of DMEK early in learning curve. The concept of a non-human ex-vivo eye model is simple and reproducible and obviates the need for human tissue and the issues of poor visibility in stored corneal tissue.

Efficient reduction of the scrolling of Descemet membrane endothelial keratoplasty grafts by engineering the medium.

The Descemet Membrane Endothelial Keratoplasty (DMEK) procedure for corneal transplantation is challenging due to the need to unscroll the donor graft within the recipient's eye. This process of unscrolling is complex, time-consuming, leads to a loss of endothelial cells and, most importantly, can negatively impact the graft's adhesion and integration with the host tissue after surgery. This problem is particularly evident when the graft is young. However, the physics behind this scrolling is not well understood, and therefore no sustainable solution is attained. Here, we propose that the concentration gradient of the medium used during transplant leads to a displacement gradient across the graft thickness, resulting in an out-of-plane folding or scrolling of the graft tissue. Using chitosan bilayer-based experimental models, it is experimentally demonstrated that this diffusion-coupled-deformation phenomenon can successfully explain why younger donor grafts tend to scroll tighter than older ones. Most importantly, we illustrate here through experiments that the medium can be engineered to reduce the scroll tightness and thus reduce the surgical inconveniences and improve post-transplant recovery. STATEMENT OF SIGNIFICANCE: This paper addresses a major issue that surgeons face while doing Descemet Membrane Endothelial Keratoplasty (DMEK) in unscrolling grafts during the graft insertion procedure. The currently used tapping method to unscroll the graft inside the patient's eye significantly reduces endothelial cell count, thus affecting its lifetime. Surprisingly, the physics behind graft scrolling is not well understood, so no sustainable solutions are proposed by the medical community. In this work, we present the underlying mechanism of DMEK graft scroll and illustrate experimentally the reason for scroll tightness through a chitosan bilayer based experiment model. Most importantly, we have successfully demonstrated that the preserving medium of the grafts can be engineered to reduce scroll tightness.

Structure-Function Relationship in Keratoconus: Spatial and Depth Vision.

Purpose: The purpose of this study was to determine changes in spatial and depth vision with increasing severity of keratoconus and to model the structure-function relationship to identify distinct phases of loss in visual function with disease severity. Methods: Best-spectacle corrected, monocular high-contrast visual acuity, contrast sensitivity function (CSF) and stereoacuity of 155 cases (16-31 years) with mild to advanced bilateral keratoconus was determined using standard psychophysical tests. Disease severity was quantified using the multimetric D-index. The structure-function relationship was modeled using linear, positive exponential, negative exponential, and logistic nonlinear regression equations. Results: The logistic regression model explained the highest proportion of variance for spatial vision, without bias in the residual plots (R2 ≥ 66%, P < 0.001). Visual acuity showed a distinct ceiling phase and a steeper loss rate with increasing D-index (1.8 units/D-index) in this model. The area under the CSF lacked this ceiling phase and had a shallower loss rate (0.28 units/D-index). Stereoacuity loss with D-index was poorly explained by all models tested (P ≤ 0.2). Cases with lower and bilaterally symmetric D-index had better stereoacuity (181.6-376 arc seconds) than those with higher D-index (>400 arc second); both were significantly poorer than controls (approximately 30 arc second). Conclusions: Vision loss in keratoconus varies with the visual function parameter tested. Contrast sensitivity may be an earlier indicator of spatial vision loss than visual acuity. Depth perception is significantly deteriorated from very early stages of the disease. Translational Relevance: The study outcomes may be used to forecast longitudinal vision loss in keratoconus and to apply appropriate interventions for timely preservation/enhancement of vulnerable visual functions.

Corneal haze following disruption of epithelial basement membrane on ultra-high-resolution OCT following femtosecond LASIK.

PURPOSE: To analyze in vivo structural properties of a case with interface haze that developed after femtosecond laser-assisted LASIK. METHODS: Case report. RESULTS: A 42-year-old man underwent uncomplicated LASIK. Four months after the surgery he developed regression of his refractive error and interface haze in both eyes. Flap thickness was calculated as 73 µm and 81 µm in the right and left eyes, respectively. A novel ultra-high-resolution spectral domain optical coherence tomography (OCT) system was used to demonstrate in vivo morphology of the cornea. On ultra-high-resolution OCT, haze was demonstrated as increased bright white reflectivity of the flap interface. Areas of focal disruption of the basement membrane and Bowman layer corresponded with the most significant areas of interface haze. CONCLUSIONS: Our results support the hypothesis that haze after femtosecond LASIK may be a result of damage to the basement membrane and Bowman layer of the cornea.

Epithelial ingrowth after LASIK: clinical characteristics, risk factors, and visual outcomes in patients requiring flap lift.

PURPOSE: To describe clinical characteristics, risk factors, and visual outcomes in patients requiring flap lift for epithelial ingrowth following LASIK. METHODS: Consecutive, noncomparative, retrospective case series of eyes requiring flap lift for epithelial ingrowth following LASIK from June 2003 through July 2011 at a tertiary care, university-based eye hospital. Main outcome measures were uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) at 1 and 3 months and recurrence of epithelial ingrowth. RESULTS: Forty-five eyes were included. Laser in situ keratomileusis retreatment was the most common etiologic factor for epithelial ingrowth (28/45 eyes [62%]). All patients were treated with flap lift and scraping. Mean logMAR UDVA at presentation was 0.28 (Snellen equivalent 20/38). Mean logMAR UDVA at 3 months was 0.17 (Snellen equivalent 20/30) with 53% of eyes 20/25 or better. Mean logMAR CDVA at 3 months was 0.06 (Snellen equivalent 20/23) with 78% of eyes 20/25 or better. Epithelial ingrowth into the central cornea portended a trend towards UDVA worse than 20/25 or worse at 3-month follow-up (hazard ratio [HR] 5.54, 95% confidence interval [CI]: 0.98-31.3, P=.05) and CDVA worse than 20/25 at 3-month follow-up (HR 4.32, 95% CI: 0.85-21.9, P=.08). Recurrence after treatment was 31% at 3 months and 36% at 1 year. Risk factors for recurrence included: infectious etiology of ingrowth (HR 5.7, 95% CI: 1.11-29.1, P=.04), use of microkeratome for primary LASIK (HR 4.64, 95% CI: 1.07-20.1, P=.04), and hyperopic primary LASIK (HR 2.49, 95% CI: 0.98-6.31, P=.06). CONCLUSIONS: Patients undergoing flap lift for the treatment of epithelial ingrowth have a relatively high rate of recurrence but good visual acuity outcomes.