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Objectives: To report the results of epithelium-off accelerated corneal collagen crosslinking (accelerated corneal crosslinking [ACXL]) in patients with progressive keratoconus., Methods: This prospective, nonrandomized, noncomparative, interventional, multicenter clinical study included all patients who underwent ACXL, either continuous (c-ACXL; 9 mW/cm 2 , 10', 5.4 J/cm 2 ) or pulsed (p-ACXL; 2″ON/1″OFF, 30 mW/cm 2 , 4.5', 5.4 J/cm 2 ) between January 2014 and May 2017. Best-corrected visual acuity, sphere, cylinder, spherical equivalent, and topographical keratometry data were collected preoperatively and at 1, 3, 6, 12, 18, and 24 months postoperatively., Results: Ninety-six eyes of 78 patients were included. The mean age was 20.8±4.4 years (14-33) for c-ACXL and 26.7±7.7 years (12-37) for p-ACXL. The mean best-corrected visual acuity was 0.4±0.4 for c-ACXL and 0.01±0.1 for p-ACXL preoperatively, and 0.3±0.3 ( P =0.0014) and -0.01±0.1 ( P =0.1554), respectively, at the last follow-up. The subjective sphere and spherical equivalent did not show statistically significant differences between the time points ( P >0.05). The subjective cylinder showed significant differences ( P =0.0013 for c-ACXL; P =0.0358 for p-ACXL). Keratometric values (K steep , K flat , and SimK) remained stable, with no statistically significant differences ( P >0.05). No major complications were noted., Conclusions: Both c-ACXL and p-ACXL are equally safe and effective ACXL protocols in stabilizing the progression of keratoconus and can be considered alternatives to the conventional Dresden protocol., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Contact Lens Association of Ophthalmologists.)

Aims: To describe clinical outcomes, management, and socio-economic impact of severe acute chemical eye injuries in a tertiary hospital., Methods: 37 patients required emergency admission to the Royal Victoria Infirmary eye ward between April 2013 and September 2015. Demographics, best corrected distance visual acuity (BCDVA), causative agent, degree of limbal stem cell deficiency (LSCD), management and socio-economic data were evaluated., Results: Mean age on admission was 34.5 years (SD 16.3; range 16-82); 30 males (81.1%); 22 bilateral (59.5%). Causative agent: alkali in 30 cases (81.1%); acid in three cases (8.1%); and unknown in four cases (10.8%). Fifteen cases (40.5%) were assaults, 12 (32.5%) work-related accidents, nine (24.3%) domestic accidents and one (2.7%) undetermined. Eleven patients (29.7%) were unemployed, 18 (48.6%) were labourers, three (8.1%) were students, three (8.1%) were retired and two (5.4%) were professionals. Mean admission time was five days (SD 3.2; range 1-12). Mean follow-up time was 170.5 days (range 1-946). Mean cost of admission was £2478 (range £274-5785). Five patients (13%; seven eyes) developed total or partial limbal stem cell deficiency, all being assaults., Conclusions: Main causative agent in our study was alkali, with young men in the working age being most frequently involved. Many patients required prolonged hospital admission and costly follow-up. The majority of cases were assaults, mostly occurring in unemployed patients. All the limbal stem cell deficiency cases were due to assaults. We believe that socio-economic factors play an important role in the cause, severity and cost of chemical eye injuries., Lay Summary: Acute chemical eye injuries have a significant and extensive impact on patients' visual function outcomes and vision-related quality of life, with consequent enormous burden to affected individuals, their families and society. We believe that by understanding the socio-economic environment, we may not only be able to enforce safety measures to tackle the increasing rate of severe chemical eye injuries in our community, but also to develop collaborative programmes with the community, educating the population on the seriousness of chemical eye injuries, and with the local authorities, trying to understand the clustering of assaults in areas and tackling the associated socio-economic risk factors, such as unemployment. Given the increasing rate of assaults using chemicals in recent times, it is also important to assess availability of adequate victim support programmes and develop good interaction with relevant local, regional and national authorities to ensure all aspects of community security service are in place to be able to address any potential deficiencies in line with police and home office guidelines. Keeping in mind that the best action plan is always prevention. However, when an ocular injury does occur it is evident that significant morbidity and visual sequelae can result and affect the socio-economic status of the victims despite our best current medical and surgical care., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Abstract: A new therapeutic alternative has been developed in the past 6 years to treat severe keratoconus in young patients. Those patients had only corneal transplantation as an option, but now a variety of surgical alternatives in the form of allogeneic corneal inclusions have bloomed and are becoming more popular. Although Bowman layer transplantation is the most studied technique, recent studies have described different options with very promising preliminary results. Mostly all the techniques described improve corneal curvature, visual acuity, pachymetry, contact lens tolerance, and foremost, manage to avoid or postpone corneal transplantation. Very few complications have been described so far, which makes these techniques not only feasible but also safe. Herein, we focus on reviewing recently published studies describing these techniques and their first results., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To assess correlation between results from both eyes of the same patient after implantation of intrastromal corneal ring segments (ICRS) and define whether they can be used together in clinical studies., Methods: A review of medical records of 74 patients with keratoconus implanted with bilateral Ferrara ICRS at Centro de Oftalmología Barraquer from January 2005 until December 2014. Data were collected on uncorrected visual acuity, best-corrected visual acuity and subjective refractive values (sphere, cylinder and axis)., Results: A total of 39 patients were male (53%), and 35 were female (47%). Mean age at the time of implantation was 32.5 ± 10 years. No major complications occurred. A significant correlation between the results from right and left eyes was found (p < 0.0043), indicating that both eyes significantly resembled each other. No significant interaction in the magnitude of change between eye and surgery was observed under classic and mixed models., Conclusion: Based on our data, whenever application is not possible under mixed-model analyses, we recommend the use of a first eye operated only, either right or left, in order to avoid bias and errors derived from autocorrelation and guarantee the independence of the registered observations., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Introduction: Mooren's ulcer is a painful, inflammatory chronic keratitis that affects corneal periphery, progressing centripetally, ultimately ending in perforation. The first line of treatment includes systemic immunomodulators, with surgery being the last option. We present a case of bilateral Boston keratoprosthesis implantation for severe Mooren's ulcer that responded differently in each eye., Clinical Case: A 32-year-old male with corneal opacification, anterior staphylomas, vision of hand movement, was started on systemic immunosuppression with cyclosporine. After two failed penetrating keratoplasties in each eye, high intraocular pressure despite diode cyclophotocoagulation, and cystic macular edema, we performed Boston keratoprosthesis type 1 in both eyes. The right eye responded initially well, with a best-corrected visual acuity of 20/80 and normal intraocular pressure. The left eye presented high intraocular pressure, which required cyclophotocoagulation, ultimately resulting in hypotony. Boston keratoprosthesis was performed but had peripheral corneal necrosis that progressed despite amniotic membrane transplantation and aggressive intensive treatment with medroxyprogesterone, autologous platelet-rich-in-growth-factors eye drops, and oral doxycycline. Thus, replacement of the semi-exposed Boston keratoprosthesis with tectonic penetrating keratoplasty was necessary. However, both eyes developed phthisis bulbi with final visual acuity of perception of light with poor localization., Conclusion: Mainstay treatment of Mooren's ulcer is systemic immunomodulation. Surgical treatment must be considered only when risk of perforation, preferably with inflammation under control. Penetrating keratoplasty frequently fails, and Boston keratoprosthesis may be a viable option. However, postoperative complications, especially uncontrolled high intraocular pressure, corneal necrosis, and recurrence of Mooren's ulcer may jeopardize the outcomes and need to be addressed promptly with intensive topical and systemic treatment.

Purpose: To report a case of a unilateral spontaneous filtering bleb dissecting into the cornea in a patient with high myopia., Clinical Case: A 33-year-old woman with high myopia (-18 D) presented with discomfort in the left eye. Ocular history included pars plana vitrectomy and cataract extraction and posterior chamber intraocular lens implantation in the left eye. Best-corrected visual acuity was 0.65 and intraocular pressure was 20 mmHg. Slit-lamp examination showed a filtering bleb in the upper-temporal quadrant, which extended and dissected the proximal cornea without affecting the visual axis. The morphology and content of the bleb was studied with anterior segment optical coherence tomography, which ruled out a corneal-scleral fistulization into the subconjunctival space. The spontaneous filtering bleb was resected surgically. Due to her high myopia, two strips of fascia lata were used to strengthen the area. In the postoperative period, a complete resection of the bleb was confirmed, without apparent leaking points and with a well-vascularized conjunctiva. No complications were noted. The patient maintained the same best-corrected visual acuity and intraocular pressure than before surgery., Conclusion: The formation of a spontaneous filtering bleb is a rare entity in patients with high myopia, whose risk increases due to their thinned sclerae. The risk is even greater if they have undergone ocular surgeries. Resection of the filtering bleb in our case halted the progression of the corneal dissection, therefore respecting the transparency of the visual axis and preserving visual acuity.

Ocular inflammation is one of the leading causes of blindness worldwide, and steroids in topical ophthalmic solutions (e.g. dexamethasone eye drops) are the mainstay of therapy for ocular inflammation. For many non-infectious ocular inflammatory diseases, such as uveitis, eye drops are administered as often as once every hour. The high frequency of administration coupled with the side effects of eye drops leads to poor adherence for patients. Drug-eluting contact lenses have long been sought as a potentially superior alternative for sustained ocular drug delivery; but loading sufficient drug into contact lenses and control the release of the drug is still a challenge. A dexamethasone releasing contact lens (Dex-Lens) was previously developed by encapsulating a dexamethasone-polymer film within the periphery of a hydrogel-based contact lens. Here, we demonstrate safety and efficacy of the Dex-Lens in rabbit models in the treatment of anterior ocular inflammation. The Dex-Lens delivered drug for 7 days in vivo (rabbit model). In an ocular irritation study (Draize test) with Dex-Lens extracts, no adverse events were observed in normal rabbit eyes. Dex-Lenses effectively inhibited suture-induced corneal neovascularization and inflammation for 7 days and lipopolysaccharide-induced anterior uveitis for 5 days. The efficacy of Dex-Lenses was similar to that of hourly-administered dexamethasone eye drops. In the corneal neovascularization study, substantial corneal edema was observed in rabbit eyes that received no treatment and those that wore a vehicle lens as compared to rabbit eyes that wore the Dex-Lens. Throughout these studies, Dex-Lenses were well tolerated and did not exhibit signs of toxicity. Dexamethasone-eluting contact lenses may be an option for the treatment of ocular inflammation and a platform for ocular drug delivery. STATEMENT OF SIGNIFICANCE: Inflammation of the eye can happen either on the ocular surface (i.e. the cornea) or inside the eye, both of which can result in loss of vision or even blindness. Ocular inflammation is normally treated by steroid eye drops. Depending on the type and severity of inflammation, patients may have to take drops every hour for days at a time. Such severe dosing regimen can lead to patients missing doses. Also, more than 95% drug in an eye drop never goes inside the eye. Here we present a contact lens that release a steroid (dexamethasone) for seven days at a time. It is much more efficient than eye drops and a significant improvement since once worn, the patient will avoid missing doses., Competing Interests: Declaration of Competing Interest JBC and DSK have a financial interest in Theroptix, a company developing a contact lens drug delivery system. They are inventors of the technology, founders of the company, and also serve as consultants. JBC's interests were reviewed and are managed by Massachusetts Eye and Ear and Partners HealthCare in accordance with their conflict of interest policies. DSK's interests were reviewed and are managed by Boston Children's Hospital in accordance with their conflict of interest policies., (Copyright © 2020. Published by Elsevier Ltd.)

Purpose: To determine incidence, demographics, management, and outcomes of topical steroid-induced ocular hypertension after penetrating keratoplasty (PKP) and to establish effects on intraocular pressure (IOP) and graft rejection when alternate corticosteroids are used., Methods: A single-center, retrospective review of 568 consecutive PKPs performed between 1997 and 2010 was conducted. Data were collected on demographics, best-corrected visual acuity, surgical indications, lens status, IOP, postoperative management, and incidence of rejection., Results: Eighty eyes (14.1%) of 74 patients were included. The most common indication was keratoconus (28.8%). Twenty-seven eyes (33.8%) were phakic, 46 (57.4%) had a posterior chamber intraocular lens, and 7 (8.8%) had an anterior chamber intraocular lens. Mean postoperative IOP increase was only significant in the anterior chamber intraocular lens group (18.7 mm Hg, SD 10.4; P = 0.02). The average time for developing hypertension was 9.8 months (SD 14.8) postoperatively, with an average IOP increase of 13.3 mm Hg (SD 5.9). Prednisolone acetate 1% was switched to rimexolone 1% in 64 eyes (80%) and to fluorometholone 0.1% in 16 eyes (20%), which alone achieved IOP normalization in 26 eyes (32.5%) (P < 0.01). Fifty-four eyes (67.5%) required additional antiglaucoma medication. An average IOP reduction of 12.3 mm Hg (SD 6.9) was achieved at an average of 2.3 months (SD 5.2) after the switch. Seventeen eyes (21%) developed glaucoma and 13 eyes (16.3%) developed graft rejection after switching formulations, with no statistically significant differences between rimexolone and fluorometholone (P > 0.05)., Conclusions: The use of alternate topical corticosteroids may be considered in cases of steroid-induced ocular hypertension after PKP because they offer good antiinflammatory prophylaxis with reduced hypertensive response.

The purpose of this case is to show the efficacy of buccal mucosa as an alternative to treat a case of severe necrotizing sclero-uveitis (NSU) associated with ocular perforation. We show a severe inflammatory NSU case that did not improve with topical treatment and scleral patch. We performed a buccal mucosa graft taken from the lower lip with excellent functional and anatomical result, with no signs of relapse of the NSU after 2 years of follow-up. Buccal mucosa can be a safe, useful, and effective alternative for the reconstruction of the scleral wall., Competing Interests: None

Intravitreal injections and implants are used to deliver drugs to the retina because therapeutic levels of these medications cannot be provided by topical administration (i.e. eye drops). In order to reach the retina, a topically applied drug encounters tear dilution, reflex blinking, and rapid fluid drainage that collectively reduce the drug's residence time on the ocular surface. Residing under the tears, the cornea is the primary gateway into the eye for many topical ophthalmic drugs. We hypothesized that a drug-eluting contact lens that rests on the cornea would therefore be well-suited for delivering drugs to the eye including the retina. We developed a contact lens based dexamethasone delivery system (Dex-DS) that achieved sustained drug delivery to the retina at therapeutic levels. Dex-DS consists of a dexamethasone-polymer film encapsulated inside a contact lens. Rabbits wearing Dex-DS achieved retinal drug concentrations that were 200 times greater than those from intensive (hourly) dexamethasone drops. Conversely, Dex-DS demonstrated lower systemic (blood serum) dexamethasone concentrations. In an efficacy study in rabbits, Dex-DS successfully inhibited retinal vascular leakage induced by intravitreal injection of vascular endothelial growth factor (VEGF). Dex-DS was found to be safe in a four-week repeated dose biocompatibility study in healthy rabbits., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose: To report the diagnosis, histological findings, and treatment of a patient who developed epithelial ingrowth after Descemet membrane endothelial keratoplasty (DMEK)., Methods: We present the case of a type 2 diabetic 60-year-old man who underwent DMEK for Fuchs dystrophy. Two months after surgery, an epithelial ingrowth in the graft-host interface was suspected. After a 3-month follow-up period in which progressive and centrifugal growth of the epithelial cells in the interface was documented, penetrating keratoplasty (PK) was performed to remove all areas of epithelial ingrowth. No evidence of recurrence was observed 1 year later., Results: Histopathologic evaluation of the corneal button obtained in the PK procedure confirmed the epithelial ingrowth in the interface between the Descemet membrane graft and the host cornea., Conclusions: Epithelial ingrowth may occur after a corneal endothelium transplant. There have been multiple reports of epithelial ingrowth after Descemet stripping automated endothelial keratoplasty, but this particular case report suggests that epithelial ingrowth may also occur after DMEK. In this case, PK solved the complication.

Purpose: To compare anatomical and functional results between three types of keratoprosthesis (KPro) in chemical injury and autoimmune disease., Methods: 70 clinically comparable cases were included as follows: Boston KPro Type 1 25 eyes, osteo-odonto-keratoprosthesis (OOKP) 23 eyes, Tibial bone KPro 22 eyes. Survival times for anatomical and functional success were evaluated with Kaplan-Meier estimations and Log-rank tests. KPro exchange was considered a complication, not as failure., Results: Prosthesis retention in chemical injury group at 5 years was 86% for OOKP, 100% for Tibial bone KPro, and 65% for Boston KPro (p = 0.09), while in the autoimmune disease group it was 66% for Tibial bone KPro and 50% for Boston KPro (p = 0.19; OOKP only one case). Functional success in the chemical injury group at 5 years was 86% for OOKP, 84% for Tibial bone KPro and 71% for Boston KPro (p = 0.38), while in the autoimmune group, it was 44% for Tibial bone KPro and 15% for Boston KPro (p = 0.15; OOKP only one case). The post-operative complications in all groups were: retinal detachment, vitreous hemorrhage, endophthalmitis, retro-prosthetic membrane, uncontrolled glaucoma, the last two being more common in Boston KPro., Conclusions: For both diagnoses, chemical injury and autoimmune diseases, there was a tendency for better long-term anatomical and functional results with Tibial bone KPro followed by OOKP and Boston KPro Type 1. However, these results were not statistically significant., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To present a new technique for treating Lisch epithelial corneal dystrophy (LECD) in cases of recurrence of the disease., Methods: We present a single case report of a 41-year-old man who presented to the cornea clinic with progressive loss of vision in the right eye. Slit-lamp examination showed a large white-gray whorl-like epithelial opacity connected to the limbus, which spread over the visual axis, affecting visual acuity. The left eye was uninvolved., Results: After epithelial debridement was performed, histological analysis showed the nonkeratinized stratified flat epithelium, coalescent cytoplasmic vacuoles in some keratinocytes, and isolated cells with granular cytoplasm and small PAS negative nuclei, which confirmed the diagnosis of LECD. Despite partially successful treatment with several sequential epithelial debridements, the patient presented with confirmed recurrence of the disease soon after every treatment. Thus, focal epitheliectomy combined with localized cauterization of the limbal focus of origin was performed. Vision returned to normal, and there were no signs of recurrence at final follow-up 2 years later., Conclusions: Simple epitheliectomy combined with focal cauterization of the limbal focus of origin can be a simple, safe, and minimally invasive option for treatment of LECD.

Purpose: To analyze the incidence, nature, outcomes, and complications of acute chemical eye injuries, including the incidence of limbal stem cell deficiency (LSCD) and to compare the 2 main classifications for ocular chemical injuries: Roper-Hall (RH) and Dua., Methods: This is a prospective, consecutive, interventional single-center study between April and October 2009 of all new patients with acute chemical eye injury presenting to the Royal Victoria Infirmary eye emergency department (EED)., Results: Of 11,683 patients who attended the EED, 98 patients (110 eyes) presented with acute chemical eye injury (60% male). This represents an estimated annual incidence of 5.6 new cases per 100,000 population. Mean age was 36.5 years (1-78; SD 17.1 years), including 7 children (age <10 years). Fifty-one patients (52%) had work-related injuries. The most common chemical agent was alkali (78%). All 4 RH grade IV cases were unilateral, assault with ammonia, and required early amniotic membrane transplantation as per the protocol, but despite full treatment, they developed total LSCD in the affected eye., Conclusions: Acute chemical eye injuries are rare. Male patients in the working age group are more prone to work-related chemical injuries, whereas young children tend to have domestic injuries. Grade I, II, and III RH and Dua chemical injuries had a very good prognosis with topical treatment only, whereas RH grade IV (Dua grade IV-VI), mainly assaults with ammonia, progressed to total/severe LSCD despite appropriate management including early amniotic membrane transplantation. The Dua classification includes conjunctival involvement, having a greater value in predicting the final clinical outcome when grading chemical eye injuries.

Purpose: To report the long-term clinical outcomes of a patient with Terrien's marginal degeneration who underwent successful peripheral corneal cross-linking (CXL) to arrest progression., Methods: Clinical assessment included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), corneal topography, anterior segment optical coherence tomography, ultrasonic pachymetry, corneal hysteresis, and corneal resistance factor. Eccentric epithelium-off CXL was performed in both eyes after limbal conjunctival resection. Following the Dresden protocol, fluence irradiation was set at 5.4 J/cm 2 , using 3 mW/cm 2 for a total exposure time of 30 minutes., Results: Nine years of postoperative follow-up showed significant bilateral improvement in visual acuity, refraction, and corneal topography with no signs of progression of Terrien's marginal degeneration. In the right eye, UDVA improved from 0.05 to 0.3 decimal and CDVA from 0.8 to 1.2 decimal, cylinder was reduced from -14.00 to -3.00 diopters (D), simulated keratometry improved from 10.50 to 3.70 D, and the thinnest point on pachymetry remained almost unchanged (from 483 to 469 μm). In the left eye, UDVA improved from 0.1 to 0.2 decimal and CDVA remained unchanged at 1.2 decimal, cylinder was reduced from -6.00 to -2.75 D, simulated keratometry improved from 5.60 to 3.30 D, and the thinnest point on pachymetry remained stable at 486 μm., Conclusions: Eccentric peripheral CXL can be a safe, noninvasive alternative therapeutic approach for the management of Terrien's marginal degeneration with peripheral thinning. [J Refract Surg. 2018;34(6):424-429.]., (Copyright 2018, SLACK Incorporated.)

The purpose of this study is to investigate the outcomes of penetrating keratoplasty (PKP) following autologous cultivated limbal epithelial stem cell transplantation (CLET). A prospective, single center, interventional cohort study investigating patients with unilateral total limbal stem cell deficiency (LSCD) treated with CLET who underwent PKP. Patients with confirmed corneal re-epithelialization > 6 months post-CLET, and with best-corrected visual acuity (BCVA) <0.3 logMAR were offered PKP. CLET survival assessed by slit lamp, corneal impression cytology (CIC), and in vivo confocal microscopy. Confirmation of corneal re-epithelialization by histological and immunocytochemical (ICC) examination of trephined corneal buttons. Mean change in best-corrected visual acuity (logMAR) following PKP and PKP survival at 12 months were calculated. Twenty patients underwent PKP. Mean time of PKP was 19 months (range 11-41 months, SD 7.26) post-CLET. Median follow-up time post-PKP was 15 months (range 1-32, SD 10.2). CIC and ICC of all corneas confirmed corneal re-epithelialization before PKP. Mean pre-PKP BCVA was 1.46 (range 0.3-2.7, SD 0.94) improving to a mean post-PKP BCVA of 0.74 (range 0-2.7, SD 0.87); mean improvement in BCVA post-PKP of 36 letters (95% CI 15.0-57.1, p = .002). Kaplan-Meier mean graft survival was 90.9% (95% CI 50.8-98.7) at 12 months. We recommend a two-stage approach with CLET followed by PKP >12 months later. Patients experienced a significant improvement in BCVA following PKP. PKP did not have a detrimental effect on CLET survival. PKP survival post-CLET is better than that reported for high risk PKP. Stem Cells 2018;36:925-931., (© 2018 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Purpose: To test whether verteporfin with a nonthermal laser increases corneal mechanical stiffness and resistance to enzymatic degradation ex vivo., Methods: Thirty human corneas (n = 5 per group) were treated with verteporfin alone (V), irradiated with nonthermal laser therapy (689 nm) alone (NTL), or received combined treatment of verteporfin with nonthermal laser therapy for 1 sequence (V+NTL1) or 6 sequences (V+NTL6) of 1 minute of NTL exposure. Positive controls were pretreated with 0.1% riboflavin/20% dextran every 3 to 5 minutes for 30 minutes and irradiated with ultraviolet light type A (λ = 370 nm, irradiance = 3 mW/cm) for 30 minutes using the Dresden protocol (R+UVA). Untreated corneas were used as negative controls. The corneal biomechanical properties were measured with enzymatic digestion, compression, creep, and tensile strength testing., Results: V+NTL6- and R+UVA-treated corneas acquired higher rigidity and more pronounced curvature than untreated corneas. The stress-strain tests showed that V+NTL6 and R+UVA corneas became significantly stiffer than controls (P < 0.005). The V+NTL6 group seemed to be slightly stiffer than the R+UVA group, although the differences were not statistically significant. V+NTL6 corneas were found to have a significantly lower absolute creep rate (-1.87 vs. -3.46, P < 0.05) and significantly higher maximum stress values (7.67 vs. 3.02 P < 0.05) compared with untreated corneas., Conclusions: Verteporfin-NTL (V+NTL6) increases corneal mechanical stiffness and resistance to enzymatic collagenase degradation. Although a clinical study is needed, our results suggest that V+NTL6 induces corneal cross-linking and corneal biomechanical changes that are similar to those induced by standard corneal collagen cross-linking.

Purpose: To describe and further analyze the long-term results in visual acuity (VA), anatomical retention, and rate of complications from patients who underwent Boston keratoprosthesis (B-Kpro) type 1 after ocular chemical burns in the Dominican Republic., Methods: A retrospective review of 42 eyes (22 OD:20 OS) of 36 patients who underwent B-Kpro type 1 implantation after severe ocular burn at Hospital Elías Santana in Santo Domingo, Dominican Republic, between April 2006 and October 2014, were included., Results: Demographics, VA, anatomical retention, and the rates of postoperative complications and concurrent surgeries were evaluated., Conclusions: The excellent anatomical retention rates and visual outcomes presented in this study support the remarkable capability of B-Kpro type 1 to restore functional VA in eyes with severe chemical injuries. However, strict control of the postoperative complications is necessary for long-term success. In conclusion, the use of a B-Kpro type 1 after severe chemical burn is a viable option in patients otherwise condemned to the high risk of failure associated with conventional corneal grafts.

Since its discovery in the years of the French Revolution, the field of keratoprostheses has evolved significantly. However, the path towards its present state has not always been an easy one. Initially discarded for its devastating complications, the introduction of new materials and the discovery of antibiotics in the last century gave new life to the field. Since then, the use of keratoprostheses for severe ocular surface disorders and corneal opacities has increased significantly, to the point that it has become a standard procedure for corneal specialists worldwide. Although the rate of complications has significantly been reduced, these can impede the long-term success, since some of them can be visually devastating. In an attempt to overcome these complications, researchers in the field have been recently working on improving the design of the currently available devices, by introducing the use of new materials that are more biocompatible with the eye. Here we present an update on the most recent research in the field.

Purpose: We tested the feasibility of using titanium to enhance adhesion of the Boston Keratoprosthesis (B-KPro), ultimately to decrease the risk of implant-associated complications., Methods: Cylindrical rods were made of poly(methyl methacrylate) (PMMA), PMMA coated with titanium dioxide (TiO 2 ) over a layer of polydopamine (PMMA TiO2 ), smooth (Ti) and sandblasted (Ti SB ) titanium, and titanium treated with oxygen plasma (Ti ox and Ti SBox ). Topography and surface chemistry were analyzed by scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). Adhesion force between rods and porcine corneas was measured ex vivo. Titanium sleeves, smooth and sandblasted, were inserted around the stem of the B-KPro and implanted in rabbits. Tissue adhesion to the stem was assessed and compared to an unmodified B-Kpro after 1 month., Results: X-ray photoelectron spectroscopy demonstrated successful deposition of TiO 2 on polydopamine-coated PMMA. Oxygen plasma treatment did not change the XPS spectra of titanium rods (Ti and Ti SB ), although it increased their hydrophilicity. The materials did not show cell toxicity. After 14 days of incubation, PMMA TiO2 , smooth titanium treated with oxygen plasma (Ti ox ), and sandblasted titanium rods (Ti SB , Ti SBox ) showed significantly higher adhesion forces than PMMA ex vivo. In vivo, the use of a Ti SB sleeve around the stem of the B-KPro induced a significant increase in tissue adhesion compared to a Ti sleeve or bare PMMA., Conclusions: Sandblasted titanium sleeves greatly enhanced adherence of the B-KPro to the rabbit cornea. This approach may improve adhesion with the donor cornea in humans as well., Translational Relevance: This approach may improve adhesion with donor corneas in humans.

Second harmonic generation is a process through which nonlinear materials such as collagen can absorb two photons and scatter one with twice the energy. Collagen upconverts 730 nm (near-IR) to 365 nm (UV) through second harmonic generation, which cleaves a molecule bound to collagen via a UV-sensitive linker., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: Amino-amide or amino-ester local anesthetics, which are currently used for topical ocular anesthesia, are short acting and may delay corneal healing with long-term use. In contrast, site 1 sodium channel blockers (S1SCBs) are potent local anesthetics with minimal adverse tissue reaction. In this study, we examined topical local anesthesia with two S1SCBs, tetrodotoxin (TTX) or saxitoxin (STX) individually or in combination with α2-adrenergic receptor agonists (dexmedetomidine or clonidine), and compared them with the amino-ester ocular anesthetic proparacaine. The effect of test solutions on corneal healing was also studied., Methods: Solutions of TTX ± dexmedetomidine, TTX ± clonidine, STX ± dexmedetomidine, dexmedetomidine, or proparacaine were applied to the rat cornea. Tactile sensitivity was measured by recording the blink response to probing of the cornea with a Cochet-Bonnet esthesiometer. The duration of corneal anesthesia was calculated. Cytotoxicity from anesthetic solutions was measured in vitro. The effect on corneal healing was measured in vivo after corneal debridement followed by repeated drug administration., Results: Addition of dexmedetomidine to TTX or STX significantly prolonged corneal anesthesia beyond that of either drug alone, whereas clonidine did not. Tetrodotoxin or STX coadministered with dexmedetomidine resulted in two to three times longer corneal anesthesia than did proparacaine. S1SCB-dexmedetomidine formulations were not cytotoxic. Corneal healing was not delayed significantly by any of the test solutions., Conclusions: Coadministration of S1SCBs with dexmedetomidine provided prolonged corneal anesthesia without delaying corneal wound healing. Such formulations may be useful for the management of acute surgical and nonsurgical corneal pain.

Background/aims: To evaluate ex vivo biomechanical and enzymatic digestion resistance differences between standard myopic laser in-situ keratomileusis (LASIK) compared with LASIK+CXL, in which high-irradiance cross-linking (CXL) is added., Methods: Eight human donor corneas were subjected to femtosecond-assisted myopic LASIK. Group A (n=4) served as a control group (no CXL). The corneas in LASIK+CXL group B were subjected to concurrent prophylactic high-irradiance CXL (n=4). Saline-diluted (0.10%) riboflavin was instilled on the stroma, subsequently irradiated with UV-A through the repositioned flap. The cornea stroma and flap specimens were separately subjected to transverse biaxial resistance measurements; biomechanical differences were assessed via stress and Young's shear modulus. Subsequently, the specimens were subjected to enzymatic degradation., Results: For the corneal stroma specimen, stress at 10% strain was 128±11 kPa for control group A versus 293±20 kPa for the LASIK+CXL group B (relative difference Δ=+129%, p<0.05). The stress in group B was also increased at 20% strain by +68% (p<0.05). Shear modulus in group B was increased at 10% strain by +79%, and at 20% strain by +48% (both statistically significant, p<0.05). The enzymatic degradation time to dissolution was 157.5±15.0 min in group A versus 186.25±7.5 min in group B (Δ=+18%, p=0.014). For the flaps, both biomechanical, as well as enzymatic degradation tests showed no significant differences., Conclusions: LASIK+CXL appears to provide significant increase in underlying corneal stromal rigidity, up to +130%. Additionally, there is significant relevant enzymatic digestion resistance confirmatory to the above. LASIK flaps appear unaffected biomechanically by the LASIK+CXL procedure, suggesting effective CXL just under the flap., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: The aim of this study was to evaluate glaucoma onset and progression after implantation of Boston Keratoprostheses (B-KPro) and the role of glaucoma surgery., Methods: Records of patients with B-KPro implantation during 2004 to 2009 were reviewed. Parameters relevant to B-KPro surgery and glaucoma status were recorded. The data were analyzed in 5 groups based on the preoperative diagnosis., Results: One hundred six eyes of 87 patients were included, and the average age was 54 ± 6.7 years. Forty-six percent were female. Eighteen eyes had a B-KPro with a titanium back plate, and the others had a poly(methyl methacrylate) back plate. Thirty-three eyes were pseudophakic, and the rest were left aphakic. The follow-up time was 3.3 ± 1.0 years. Indications for implantation included past infection, congenital glaucoma, trauma, autoimmune diseases, aniridia, burns, and others. Sixty-six percent of the eyes had glaucoma preoperatively, and 26% developed de novo glaucoma afterward. The mean intraocular pressure (by finger palpation) was 16.5 ± 5.7 mm Hg. Reliable visual field tests were only available in 59% of the eyes; hence, the cup-to-disc ratio of the optic nerve head was used as the main outcome measure. In B-KPro-implanted eyes with glaucoma, 65% had undergone glaucoma surgery at some point, and 30% did not show progression. Thirty-one percent of the total cohort had disc pallor with a cup-to-disc ratio of <0.8., Conclusions: Glaucoma in B-KPro remains a challenge, despite aggressive attempts to slow down its progression. Patients with glaucoma before B-KPro implantation should be considered for glaucoma surgery before or simultaneously with B-KPro implantation. The high number of eyes with disc pallor suggests that additional mechanisms other than elevated intraocular pressure may play a role in optic neuropathy.

Purpose: The aim of this study was to assess the possibility of light damage to the retina by a surgical microscope during implantation of a Boston Keratoprosthesis (B-KPro) in rabbits., Methods: The retinal irradiance from a Zeiss OPMI Lumera S7 operating microscope was measured at the working distance (16.5 cm). Light transmittance through an isolated B-KPro was measured. A B-KPro was implanted into 1 eye of 12 rabbits with the optic covered during the procedure. The operated eyes were then continuously exposed to a fixed light intensity under the microscope for 1 hour. Fluorescein angiography was carried out on days 2 and 9 postsurgery, after which the animals were euthanized. Further, we compared the potential of these retinal exposures to well-accepted light safety guidelines applicable to humans., Results: Light transmittance of B-KPro revealed a blockage of short wavelengths (<390 nm) and of long wavelengths (1660-1750 nm) of light. In addition, the surgical microscope filtered a part of the blue, ultraviolet, and infrared wavelengths. Neither fluorescein angiography nor a histological examination showed any morphological retinal changes in our rabbits. Moreover, the retinal exposures were well below the safety limits., Conclusions: Modern surgical microscopes have filters incorporated in them that block the most damaging wavelengths of light. The B-KPro is made of 100% poly(methyl methacrylate), which makes it in itself a blocker of short wavelengths of light. No damage could be demonstrated in the animal study, and the retinal exposures were well below the safety limits. Together, these results suggest that light exposures during B-KPro surgery present a low risk of photochemical damage to the retina.

For nearly half a century, contact lenses have been proposed as a means of ocular drug delivery, but achieving controlled drug release has been a significant challenge. We have developed a drug-eluting contact lens designed for prolonged delivery of latanoprost for the treatment of glaucoma, the leading cause of irreversible blindness worldwide. Latanoprost-eluting contact lenses were created by encapsulating latanoprost-poly(lactic-co-glycolic acid) films in methafilcon by ultraviolet light polymerization. In vitro and in vivo studies showed an early burst of drug release followed by sustained release for one month. Contact lenses containing thicker drug-polymer films demonstrated released a greater amount of drug after the initial burst. In vivo, single contact lenses were able to achieve, for at least one month, latanoprost concentrations in the aqueous humor that were comparable to those achieved with topical latanoprost solution, the current first-line treatment for glaucoma. The lenses appeared safe in cell culture and animal studies. This contact lens design can potentially be used as a treatment for glaucoma and as a platform for other ocular drug delivery applications., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: To present a novel design of an implantable glaucoma valve based on ferrofluidic nanoparticles and to compare it with a well-established FDA approved valve., Setting: Massachusetts Eye & Ear Infirmary, Boston, USA., Methods: A glaucoma valve was designed using soft lithography techniques utilizing a water-immiscible magnetic fluid (ferrofluid) as a pressure-sensitive barrier to aqueous flow. Two rare earth micro magnets were used to calibrate the opening and closing pressure. In-vitro flow measurements were performed to characterize the valve and to compare it to Ahmed™ glaucoma valve. The reliability and predictability of the new valve was verified by pressure/flow measurements over a period of three months and X-ray diffraction (XRD) analysis over a period of eight weeks. In vivo assessment was performed in three rabbits., Results: In the in vitro experiments, the opening and closing pressures of the valve were 10 and 7 mmHg, respectively. The measured flow/pressure response was linearly proportional and reproducible over a period of three months (1.8 µl/min at 12 mmHg; 4.3 µl/min at 16 mmHg; 7.6 µl/min at 21 mmHg). X-ray diffraction analysis did not show oxidization of the ferrofluid when exposed to water or air. Preliminary in vivo results suggest that the valve is biocompatible and can control the intraocular pressure in rabbits., Conclusions: The proposed valve utilizes ferrofluid as passive, tunable constriction element to provide highly predictable opening and closing pressures while maintaining ocular tone. The ferrofluid maintained its magnetic properties in the aqueous environment and provided linear flow to pressure response. Our in-vitro tests showed reliable and reproducible results over a study period of three months. Preliminary in-vivo results were very promising and currently more thorough investigation of this device is underway.