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Hanefi Cakir1, Canan Asli Utine2, Mehmet Baykara31Turkiye Hospital Eye Clinic, Istanbul, 2Department of Ophthalmology, Yeditepe University, Istanbul, 3Department of Ophthalmology, Uludag University, Bursa, TurkeyPurpose: To report the use of intracorneal ring segment (ICRS) implantation in a case of severe corneal thinning and irregularity secondary to alkali burn.Case report: A 33-year-old man who had a history of ocular alkali burn in the right eye was admitted. His best corrected visual acuity was 0.16 with manifest refraction of +5.00 (-7.00 × 180°). Orbscan II® revealed steepening of >53 D superiorly, excessive thinning inferiorly with thinnest pachymetric reading of 269 µm. Two KeraRing® segments, 200 µm thick and 90° arced, were implanted. During intrastromal channel creation by Intralase®, the inferior half of the applanating cone was covered by a gelatinous paper to prevent the penetration of the laser beam into the anterior chamber. In the first year postoperation, best corrected visual acuity was 0.7 with manifest refraction of +1.50 (-3.50 × 35°). Visante® opticial coherence tomography displayed ICRS at a depth of ~370 µm.Conclusion: ICRS implantation with this novel approach may be an option in eyes with severe corneal irregularity and thinning.Keywords: alkali burn, ectasia, intrastromal corneal ring segments

Canan Asli UtineYeditepe University, Department of Ophthalmology, Istanbul, Turkey and Ocular Surface Disease and Dry Eye Clinic, Cornea and External Disease Service, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USAAbstract: Azithromycin is an azalide that acts by binding to the 50S ribosomal subunit of susceptible microorganisms and interfering with microbial protein synthesis. Azithromycin is also noted by anti-inflammatory and immunomodulatory activity. AzaSite® (Inspire Pharmaceuticals, Inc, Durham, NC) is azithromycin ophthalmic solution, 1% formulated in polycarbophil (the aqueous mucoadhesive polymer contained in DuraSite®) that delivers high and prolonged azithromycin concentrations in a variety of ocular tissues, including the conjunctiva, cornea and particularly the eyelid. AzaSite was approved by the Food and Drug Administration (FDA) in the US in 2007, for the treatment of bacterial conjunctivitis caused by susceptible isolates. This article aims to evaluate the peer-reviewed published scientific literature and to define well-established uses of AzaSite eye drops in the field of ocular infections.Keywords: azithromycin, AzaSite, DuraSite

Utine CA. Update and critical appraisal of the use of topical azithromycin ophthalmic 1% (AzaSite®) solution in the treatment of ocular infections. Clin Ophthalmol. 2011;5:801-809.Table 2 inaccurately states that Bremond-Grignac used AzaSite® in their study. The ophthalmic preparation used was in fact Azyter®. Original Article

We present the case of a 37-year-old woman who underwent bilateral penetrating keratoplasty for congenital hereditary endothelial dystrophy at the age of 10 years. Over the subsequent 27 years, the patient's vision slowly deteriorated. Our examination revealed decompensation of the right corneal graft. We addressed this with regraft surgery. We then learned that the patient had been suffering from progressive hearing loss since adolescence. Tonal audiometry revealed hearing per ceptive deafness of 25 dB, which was more prominent in the left ear. Because the patterns of progressive sensorineural hearing loss and congenital hereditary endothelial dystrophy have both been linked to the same gene, slc4a11, we tested our patient for mutations in this gene. The test was positive for a heterozygous slc4a11 gene fifth exon mutation on chromosome 20p13-p12, which causes a frameshift. A combined clinical and genetic evaluation confirmed a diagnosis of Harboyan syndrome. After the genetic diagnosis of the disease, she was evaluated for the need for a hearing aid due to her hearing loss. The patient was also informed about genetic counseling.

We present a case of presumed xeroderma pigmentosum (XP) with concomitant foveal hypoplasia. A 50-year-old male patient with extensive bilateral symblepharon-like pseudopterygia was referred for visual rehabilitation. After dermatology consultation and ophthalmologic examination, presumed XP was diagnosed. Optical coherence tomography revealed grade 2 foveal hypoplasia. The patient was referred for genetic testing because concomitant XP and foveal hypoplasia are rare. The genetic test results revealed mutations in some genes, including the hemochromatosis genes HFE, COL1A2, Lysosome Trafficking Regulator (LYST), NF1, and HMBS. The LYST gene is known to be associated with foveal hypoplasia. Since the association of foveal hypoplasia and XP has been reported in another case in the literature, we present our case to share this rare association., Competing Interests: Conflict of Interest: None declared.

Tissue engineering (TE) is a field of science that combines biological, engineering, and medical sciences and allows the development of disease models, drug development and gene therapy studies, and even cellular or tissue-based treatments developed by engineering methods. The eye is an organ that is easily accessible and amenable to engineering applications, paving the way for TE in ophthalmology. TE studies are being conducted on a wide range of topics, including the tear film, eyelids, cornea, optic nerve, glaucoma, and retinal diseases. With the rapid scientific advances in the field, it seems that TE is radically modifying the management of ocular disorders., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2024 by the Turkish Ophthalmological Association / Turkish Journal of Ophthalmology published by Galenos Publishing House.)

Ophthalmic diseases affect many people, causing partial or total loss of vision and a reduced quality of life. The anterior segment of the eye accounts for nearly half of all visual impairment that can lead to blindness. Therefore, there is a growing demand for ocular research and regenerative medicine that specifically targets the anterior segment to improve vision quality. This study aims to generate a microfluidic platform for investigating the formation of the anterior segment of the eye derived from human induced pluripotent stem cells (hiPSC) under various spatial-mechanoresponsive conditions. Microfluidic platforms are developed to examine the effects of dynamic conditions on the generation of hiPSCs-derived ocular organoids. The differentiation protocol is validated, and mechanoresponsive genes are identified through transcriptomic analysis. Several culture strategies is implemented for the anterior segment of eye cells in a microfluidic chip. hiPSC-derived cells showed anterior eye cell characteristics in mRNA and protein expression levels under dynamic culture conditions. The expression levels of yes-associated protein and transcriptional coactivator PDZ binding motif (YAP/TAZ) and PIEZO1, varied depending on the differentiation and growth conditions of the cells, as well as the metabolomic profiles under dynamic culture conditions., (© 2024 Wiley‐VCH GmbH.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Competing Interests: Conflict of Interest: None declared.

Purpose: To describe the frequency, clinical characteristics, complications, and management of glaucoma in eyes that underwent keratoprosthesis implantation., Methods: Patients who underwent keratoprosthesis surgery between June 2010 and January 2020 were retrospectively evaluated for glaucoma association and prognoses., Results: Among 17 patients who underwent keratoprosthesis surgery, 9 (52.9%) were associated with underlying or keratoprosthesis-induced glaucoma. Five eyes (29.4%) had underlying glaucoma and underwent a glaucoma drainage device implantation at least 6 months before keratoprosthesis surgery. One eye (5.9%) with normal intraocular pressure had glaucoma drainage device implantation at the same session with keratoprosthesis surgery due to high-risk characteristics of anterior segment structures. Four eyes with preexisting glaucoma showed progression after keratoprosthesis surgery. Additional antiglaucomatous treatment was commenced in two eyes whereas implantation of 2nd glaucoma drainage device was performed in two eyes. Postoperative complications in three eyes (100%) with glaucoma drainage device implanted 6 months before or at the same session with aphakic type keratoprosthesis surgery with partial vitrectomy included rhegmatogenous retinal detachment in two eyes and bacterial endophthalmitis in one eye. Migration of silicone oil through the tube to the subconjunctival area was seen after pars plana vitrectomy in one eye. None of the three eyes (0%) that underwent glaucoma drainage device implantation years before keratoprosthesis surgery experienced a posterior segment complication other than glaucomatous progression. Out of 11 eyes with no previous history of glaucoma, 3 (27.3%) showed high intraocular pressure and glaucomatous disc changes after keratoprosthesis surgery, which could be pharmacologically controlled., Conclusions: In this cohort, eyes with preexisting glaucoma were more difficult to manage compared to eyes with de novo glaucoma after keratoprosthesis surgery. Retinal complications appeared more often when glaucoma drainage device implantation was performed no more than 6 months before aphakic type keratoprosthesis surgery with partial vitrectomy.

Lacrimal gland plays a vital role in maintaining the health and function of the ocular surface. Dysfunction of the gland leads to disruption of ocular surface homeostasis and can lead to severe outcomes. Approaches evolving through regenerative medicine have recently gained importance to restore the function of the gland. Using human induced pluripotent stem cells (iPSCs), we generated functional in vitro lacrimal gland organoids by adopting the multi zonal ocular differentiation approach. We differentiated human iPSCs and confirmed commitment to neuro ectodermal lineage. Then we identified emergence of mesenchymal and epithelial lacrimal gland progenitor cells by the third week of differentiation. Differentiated progenitors underwent branching morphogenesis in the following weeks, typical of lacrimal gland development. We were able to confirm the presence of lacrimal gland specific acinar, ductal, and myoepithelial cells and structures during weeks 4-7. Further on, we demonstrated the role of miR-205 in regulation of the lacrimal gland organoid development by monitoring miR-205 and FGF10 mRNA levels throughout the differentiation process. In addition, we assessed the functionality of the organoids using the β -Hexosaminidase assay, confirming the secretory function of lacrimal organoids. Finally, metabolomics analysis revealed a shift from amino acid metabolism to lipid metabolism in differentiated organoids. These functional, tear proteins secreting human lacrimal gland organoids harbor a great potential for the improvement of existing treatment options of lacrimal gland dysfunction and can serve as a platform to study human lacrimal gland development and morphogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Asal, Koçak, Sarı, Reçber, Nemutlu, Utine and Güven.)

Aqueous tears secreted by the lacrimal gland have vital importance in maintaining and protecting the ocular surface health. Serious complications such as corneal ulceration, ocular surface keratinization and permanent vision loss can be seen in aqueous deficiency type dry eye disease that develops as a result of irreversible damage in the lacrimal gland. Current treatment options offer only short-term temporary palliation to reduce pain and inflammation on the ocular surface with no long-term improvement in lacrimal gland function. In recent years, the cellular and molecular properties of the lacrimal gland have been better understood, and studies carried out in the field of regenerative medicine show promise for the principal treatment of serious aqueous deficiency dry eye disease. In partial lacrimal gland damage, in situ regeneration can be achieved by using stem cells in the tissue. In total gland damage, healing can occur as a result of transplantation of organoids developed from induced pluripotent stem cells (iPSC) thanks to the tissue engineering method. Here, it is aimed to review the appropriate cellular resources for regeneration and development of functional artificial lacrimal gland by comparing studies using in situ stem cells and iPSC., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate ocular surface manifestations in patients with acne rosecea (AR) and to find out main features indicating a propensity toward an association with disease diagnosis., Methods: Right eyes of consecutive 76 AR patients and 113 age-gender matched healthy subjects were enrolled. Ophthalmologic examinations including tear break-up time (t-BUT) and Schirmer-2 tests to analyze tear film insufficiency, optical coherence tomography (OCT)-assisted infrared meibography to analyze meibomian gland drop-out, and Ocular Surface Disease Index (OSDI) questionnaire were performed in all participants., Results: No statistically differences were found in visual acuity, intraocular pressure, central corneal thickness, and axial length assessments between the study and control eyes. Study eyes had more foreign body sensation, itching, dryness, hyperemia, conjunctival telangiectasia, and meibomitis (p ≤ 0.005, for all). Significantly higher t-BUT and Schirmer-2 tests; lower-eyelid and total OCT meibography; and OSDI scores were found in AR patients (p < 0.05, for all). Among all, only conjunctival telangiectasia (p = 0.001; OR:0.070, 95% CI:0.015-0.330) was found to be major independent predictor for AR diagnosis., Conclusion: Detailed slit-lamp examination to detect any conjunctival telangiectasia seems to be crucial in recalcitrant dry eye cases, not to miss underlying AR. Especially, lower-eyelid OCT meibography score may be sensitively used for disease staging., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Vitreoretinal surgery in eyes with Boston type 1 keratoprosthesis (KPro) is challenging due to narrow optic of the KPro. This study analyzed the results of pars plana vitrectomy (PPV) using a wide-field imaging accessory, Resight®700 Fundus Viewing System (Carl Zeiss Meditec, Inc., Germany), for better intraoperative peripheral retinal imaging., Methods: In this retrospective case series, KPro patients who underwent simultaneous or sequential PPV at Dokuz Eylul University Hospital between June 2010 and January 2020 were evaluated in terms of anatomic and visual prognoses, as well as KPro- and PPV-associated complications., Results: Among 9 KPro eyes that necessitated vitreoretinal surgery, 3 (33.3%) underwent simultaneous KPro and PPV due to proliferative vitreoretinopaties; 6 (66.7%) underwent PPV for retinal detachment or suprachoroidal hemorrhage that appeared after KPro surgery. Retina could be attached in 7 eyes (77.8%), and vision improved in 3 eyes (33.3%). In 1 eye, injected silicone oil moved to subconjunctival area through glaucoma drainage device., Conclusion: In eyes with a Boston KPro, wide-angle viewing systems helped handling peripheral retinal problems successfully during PPV, with no observed inadequacy of imaging. Despite anatomical success in most cases, visual prognosis depends on vitality of the macula and the optic disc., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To evaluate the clinical outcomes of pseudophakic/aphakic eyes with uncontrolled glaucoma that underwent Ahmed glaucoma valve implantation with the tube placement in the ciliary sulcus., Methods: Medical records of the patients who underwent Ahmed glaucoma valve implantation through the ciliary sulcus, between December 2017 and June 2019, were reviewed retrospectively. Patients' age, gender, glaucoma diagnosis, visual acuity, intraocular pressure levels, and complications were recorded., Results: Forty-seven eyes of 43 patients with glaucoma were enrolled. The mean age was 54.5 ± 19.9 years (range, 7-88 years) at the time of surgery, and the mean postoperative follow-up period was 7.9 ± 3.4 months (range, 3-16 months). The mean preoperative intraocular pressure level was 35.2 ± 6.8 mmHg (range, 25-55 mmHg), and it was found as 15.6 ± 5.4 mmHg (range, 9-33 mmHg) at the last follow-up visit. Decrease in intraocular pressure level was statistically significant (P < 0.001). At the last follow-up visit, success (postoperative IOP ≥ 6 mmHg and ≤ 21 mmHg with or without antiglaucomatous medications, without further surgery for IOP control, without loss of light perception and without removal of the implant) was achieved in 41 eyes (87.2%). Hyphema was the most common postoperative complication and developed in 11 eyes (23.4%) and resolved spontaneously in all of them within one month., Conclusion: In pseudophakic or aphakic eyes with uncontrolled glaucoma, placement of Ahmed glaucoma valve tube in the ciliary sulcus is a safe and effective procedure. Ciliary sulcus can be considered as a potential space during tube shunt surgery in eyes with high risk of tube-corneal touch or corneal decompensation., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To report three consecutive cases with noninfectious corneal melting, whose disease progression could only be halted with tumor necrosis-α (TNF-α) inhibitor infusion, with a review of the relevant literature., Materials and Methods: Patients with toxic epidermal necrolysis, severe alkaline burn, and Sjögren syndrome had experienced severe corneal melting following penetrating keratoplasty, Boston type 1 keratoprosthesis implantation or spontaneously, respectively. Topical autologous serum eye-drops, medroxyprogesterone, and acetylcysteine formulations; frequent nonpreserved lubrication; systemic tetracyclines and vitamin-C supplements; topical and systemic steroids and steroid-sparing agents; surgical approaches including amniotic membrane transplantation, tectonic graft surgery; and tarsorraphy failed to alter the disease courses., Results: Upon consultation with the rheumatology clinic, TNF-α inhibitor infliximab (Remicade; Centocor Ortho Biotech Inc, Horsham, PA) 5 mg/kg infusion was planned for each patient. After 0-, 2-, and 6-week doses, monthly infusion at the same dose was maintained for 12 months because of severe and intractable course of their diseases. Each case showed dramatic improvements in corneal melts; and sterile vitritis in the eye with Boston keratoprosthesis responded, as well., Conclusions: Inhibiting TNF-α-mediated expression of matrix metalloproteinases responsible for collagen breakdown should be considered in refractory cases, as a means of globe salvage., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Contact Lens Association of Ophthalmologists.)

Background: To compare the results of single versus double intracorneal ring segment (ICRS) (KeraRing) implantation in keratoconus with respect to different cone locations., Methods: Twenty-two eyes of 18 patients with totally asymmetric cones (20-80% or 0-100% distribution along steep axis) were implanted with single ICRS (Group 1), 38 eyes of 32 patients with central or partially asymmetric cones (50-50% or 40-60% distribution along steep axis) were implanted with double ICRS (Group 2), at a depth of 80% of the site of implantation, in channels created with femtosecond laser device. All patients had uncorrected and corrected distance visual acuities (UDVA and CDVA, respectively) of ≤ 0.3 Snellen lines., Results: In both groups, patients had median UDVA and CDVA gain of 3 Snellen lines (P > 0.05). Postoperative improvement in indices of vertical asymmetry and height decentration in Group 1; simulated keratometry, corneal astigmatism and anterior corneal asphericity values in Group 2 were greater (P < 0.05). A total of 10 eyes (45.5%) in Group 1 were recommended double ring implantation by the manufacturer's nomogram, but underwent single ICRS implantation and achieved visual, refractive, tomographic outcomes comparable to that in Group 2, although corneal cylindrical correction was less and final topographic astigmatism was greater., Conclusion: Double ICRS implantation seems to be superior in terms of keratometry, corneal astigmatism and anterior corneal asphericity improvement. Single ICRS implantation in totally asymmetric cones seems to provide satisfactory visual, refractive and tomographic results, similar to double ICRS implantation in central and partially asymmetric cones, by inducing central shift of the cone.

Objectives: To report real-world long-term survival of primary penetrating keratoplasty (PK) in the United States and analyze risk factors associated with failure., Design: Retrospective longitudinal cohort study using a large commercial insurance database., Participants: Ten million patients enrolled in the database from 2011 to 2017 were identified using Current Procedural Terminology codes for PK., Methods: Kaplan-Meier survival analysis was performed to determine failure rate and risk factors impacting graft outcomes., Results: Five hundred and ninety-six primary PKs were identified. The 3-year survival was 78% (confidence interval [CI]: 73%-82%), 5-year survival was 76% (CI: 70%-80%), and 7-year survival was 73% (CI: 66%-79%)., Conclusion: This study demonstrated a significantly lower 5-year success rate for primary PK performed for all causes than previously published case series in the United States., (Copyright © 2020 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Dupilumab is the first US FDA approved biologic for treatment of atopic dermatitis. It is a human monoclonal antibody which blocks the shared receptor component, the interleukin (IL)-4α subunit, of IL-4 and IL-13 signaling pathways. Occurrence of "conjunctivitis", mostly in atopic dermatitis trials, has been the main side effect reported thus far. The etiology of "conjunctivitis" associated with dupilumab treatment is unclear and might be similar to atopic keratoconjunctivitis. There is evidence in the published literature that unlike the Th2-like profile in vernal keratoconjunctivitis, Th1-mediated inflammation is predominant in atopic keratoconjunctivitis. Blocking the Th2 pathway with dupilumab therapy might result in a shift towards Th1, causing the ocular findings associated with dupilumab. In addition, blockage of IL-13 might have implications with regards to mucin production and ocular surface health. This review highlights the clinical manifestations, reviews treatment options and offers explanations for pathogenesis of this ocular surface diseases associated with dupilumab treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To assess differential roles of inflammatory cells in pathophysiology of severe atopic keratoconjunctivitis (AKC) and evaluate immunomodulatory effects of topical cyclosporine A (CsA)., Methods: A total of 10 patients with severe, steroid-dependent/resistant chronic active AKC were treated using frequent topical CsA 0.05% as monotherapy for 2 months. Conjunctival biopsy specimens before and after treatment were examined using immunohistochemistry. A total of 10 healthy age-matched adults served as the control group., Results: Baseline AKC samples revealed greater cluster of differentiation 4 (CD4), interferon gamma (IFNγ), human leukocyte antigen-D-related (HLA-DR) positive cell densities compared with healthy controls ( P  < 0.05), as well as interleukin (IL)-17 ( P  = 0.08). Topical CsA treatment induced a significant reduction in CD4 and IL-17 expressions ( P  < 0.05); post-treatment levels were same as normals ( P  > 0.05). Despite reduction after treatment ( P  = 0.06), HLA-DR expression remained higher than controls ( P  < 0.05)., Conclusions: AKC-related conjunctival inflammation appears to be mediated by delayed hypersensitivity. In this short-term trial, frequent topical CsA improved conjunctival inflammation.

Purpose: To identify the risk of inducing ocular surface dysplasia following topical administration of 1% voriconazole eye drop., Methods: Fourteen noninflamed healthy eyes of 14 white adult New Zealand rabbits were included in the study. The rabbits were randomly divided into two groups comprised of 7 rabbits each. Group 1 received topical 1% voriconazole and Group 2 received topical saline as the control group. In all animals, right eye was selected for the study. In Group 1 (Voriconazole Group), single drop of voriconazole was instilled every 10 min consecutively for 17 times a day for 60 days. In Group 2 (Control Group), single drop of saline was instilled every 10 min consecutively for 17 times a day for 60 days. At two months, animals were sacrificed and study eyes were enucleated with the eyelids. The specimens were stained with hematoxylin-eosin and histopathologic changes in cornea, bulbar and palpebral conjunctiva were evaluated under light microscope., Results: There were no macroscopically visible lesions on the ocular surface of any rabbits. Histopathological evaluation showed mild to moderate dysplasia localized mainly in the limbus and extending to the adjacent cornea and bulbar conjunctiva in all rabbits in Voriconazole Group. Severe dysplasia or carcinoma in situ was not observed. In the Control Group, dysplasia was not observed, at all., Conclusion: This animal study provides a possible relationship between topically administered 1% voriconazole and ocular surface dysplasia. We recommend ophthalmologists to be aware of the risk of ocular surface dysplasia in patients received voriconazole eye drop.

Purpose: Evaluation of the etiopathogenesis and management of topographic reverse pellucid pattern after rigid intraocular lens (IOL) implantation with wide limbal clear corneal incision (CCI)., Methods: Fifteen eyes with a history of gradual decrease in vision after IOL surgery with at least 6.5-mm CCI were diagnosed with wound dehiscence and were managed with tight resuturation, delayed, and selective suture removal. The improvement in uncorrected and corrected distance visual acuities (UDVA and CDVA, respectively) and refractive errors were analyzed, at least 6 months postoperatively., Results: Postoperatively, UDVA improved in 13/15 eyes (86.7%), whereas CDVA also improved for at least 2 Snellen lines in 11/15 eyes (73.3%) (P<0.01 for both). In all patients, against-the-rule astigmatism changed to with-the-rule astigmatism pattern and the amount of cylinder decreased as the sutures are removed progressively. Vector analysis of astigmatism showed an arithmetic mean of corrected amount of cylinder of 4.17±2.10 D using manifest refraction data and 4.90±2.83 D using keratometric data at the last follow-up., Conclusion: Low visual acuity together with high astigmatism after rigid IOL surgery should prompt the surgeon for considering wound dehiscence that could be managed by careful and deliberate wound revision.

Objectives: To assess the corneal topometric parameters that can be predictive for better visual gain after intracorneal ring segment (ICRS) implantation in eyes with keratoconus., Methods: A total of 42 eyes of 32 patients who underwent ICRS implantation at Dokuz Eylul University, Deparment of Ophthalmology, Cornea Divison were included. Changes in uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refractive errors, and corneal topometric indices measured using Scheimpflug topography (Pentacam, Oculus) were evaluated retrospectively., Results: After creation of intrastromal tunnels of 5.01±0.03 mm inner diameter, 5.71±0.03 mm outer diameter and at 384.21±34.12 μm depth, 1 or 2 ICRS of 150 to 350 µm thickness and 90 to 210° arc length were implanted. Preoperative UDVA of 0.09±0.10 and CDVA of 0.29±0.14 Snellen lines improved postoperatively to 0.42±0.26 and 0.62±0.24, respectively (P<0.001 for both). Preoperative spherical equivalent of -6.35±4.58D and refractive astigmatism of -5.89±2.40D decreased to -3.59±3.86 and -2.25±1.66D, retrospectively (P<0.001 for both). Strong negative correlations were detected between preoperative mean simulated keratometry (SimKavg)/index of surface variance (ISV) and changes in UDVA/CDVA (P<0.01, for all). Postoperative change in ISV was positively correlated with thicknesses of implanted rings. Change in topographical keratoconus classification was positively and change in index of vertical asymmetry was negatively correlated with number of implanted rings (P<0.05 for all)., Conclusions: Preoperative ISV value seems to be beneficial in predicting visual gain after ICRS implantation, in addition to SimKavg. Future work on new nomograms for ICRS selection that include ISV, besides refractive, topographic, and cone location data, is warranted.

Aim: To evaluate the visual, refractive and corneal asphericity changes after intrastromal corneal ring segment (ICRS) implantation for visual rehabilitation of keratoconus., Methods: A total of 42 eyes of 32 patients were included. After creation of intrastromal tunnels of 5.01±0.03 mm inner diameter, 5.71±0.03 mm outer diameter and at 384.21±34.12 µm depth, 1 or 2 ICRS of 150-300 µm thickness and 90°-210° arc length were implanted. Changes in uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refractive errors, mean simulated keratometry readings (SimK avg ), anterior and posterior corneal asphericity values (Q ant and Q post , respectively) measured with Scheimpflug topography were evaluated retrospectively., Results: There was a significant improvement in UDVA and CDVA, along with a significant decrease in refractive spherical equivalent (SE), cylinder and SimK avg postoperatively ( P <0.001 for all). Mean Q ant increased from -1.06±0.48 to -0.57±0.58 postoperatively ( P <0.001). Change in mean Q post was insignificant ( P =0.92). Postoperative changes in UDVA and CDVA were not correlated with the postoperative changes in SE and cylinder ( P >0.05 for all); but were correlated with the preoperative SimK avg and Q ant values ( P <0.001 for all)., Conclusion: ICRS implantation seems to approximate the anterior corneal asphericity of "advanced prolate" shape to "optimal prolate" shape and an "ideal Q value" of -0.46; which may have a role in improved UDVA and CDVA postoperatively, besides decreased refractive cylinder values.

Orbital apex syndrome is a rare complication of herpes zoster ophthalmicus. A patient being followed in our clinic for herpes zoster ophthalmicus developed orbital apex syndrome in the second week of treatment. Clinical diagnosis was supported by magnetic resonance imaging. Treatment with systemic steroid and antiviral therapy resulted in total regression of ophthalmoplegia at 2 months. However, optic neuropathy-induced vision loss was permanent. This case report examines orbital apex syndrome secondary to herpes zoster ophthalmicus, which has rarely been documented in the ophthalmic literature., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Background/aims: To evaluate the impact of dry eye on reading performance., Methods: Out-loud and silent reading in patients with clinically significant dry eye (n=41) and controls (n=50) was evaluated using standardised texts. Dry eye measures included tear film break-up time, Schirmer's test and corneal epithelial staining. Symptoms were assessed by the Ocular Surface Disease Index (OSDI)., Results: The dry eye group had a greater proportion of women as compared with the control group but did not differ in age, race, education level or visual acuity (p≥0.05 for all). Out-loud reading speed averaged 148 words per minute (wpm) in dry eye subjects and 163 wpm in controls (p=0.006). Prolonged silent reading speed averaged 199 wpm in dry eye subjects versus 226 wpm in controls (p=0.03). In multivariable regression models, out-loud and sustained silent reading speeds were 10 wpm (95% CI -20 to -1 wpm, p=0.039) and 14% (95% CI -25% to -2%, p=0.032) slower, respectively, in dry eye subjects as compared with controls. Greater corneal staining was associated with slower out-loud (-2 wpm/1 unit increase in staining score, 95% CI =-3 to -0.3 wpm) and silent (-2%, 95% CI -4 to -0.6 wpm) reading speeds (p<0.02 for both). Significant interactions were found between OSDI score and word-specific features (longer and less commonly used words) on out-loud reading speed (p<0.05 for both)., Conclusions: Dry eye is associated with slower out-loud and silent reading speeds, providing direct evidence regarding the functional impact of dry eye. Reading speed represents a measurable clinical finding that correlates directly with dry eye severity., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: To evaluate the effect of transepithelial corneal collagen cross-linking (CXL) with prolonged riboflavin application by in vivo confocal microscopy and to compare this effect with that of standard CXL with complete epithelial debridement., Methods: In eyes with progressive keratoconus, CXL procedure was performed with standard technique and transepithelial technique after prolonged riboflavin drop application for 2 hr. Patients were evaluated with in vivo confocal microscopic examination preoperatively and at postoperative months 1 and 6., Results: The depth of CXL effect was similar in both groups (i.e., 380.86 ± 103.23 μm in standard CXL group and 342.2 ± 68.6 μm in transepithelial CXL group) (P=0.4). The endothelial cell counts and morphological parameters (i.e., pleomorphism and polymegathism) were not significantly affected in both groups (P>0.05 for all). In the standard CXL group, in vivo confocal microscopy revealed anterior stromal acellular hyperreflective honeycomb edema with posteriorly gradually decreasing reflectivity and increasing number of keratocytes and some sheets of longitudinally aligned filamentary deposits. The keratocytes were seen to repopulate in the posterior-to-anterior direction. In transepithelial CXL group, although the depth of CXL effect was similar, less pronounced keratocyte damage, extracellular matrix hyperreflectivity, and sheets of filamentary deposits at the posterior stroma was observed., Conclusions: Transepithelial CXL with prolonged peroperative riboflavin application can achieve similar depth of effect in the stroma with less pronounced confocal microscopic changes as compared with the standard CXL with complete epithelial debridement.

Purpose: To evaluate the subjective and objective measures of ocular surface disease in patients with glaucoma., Design: Cross-sectional study., Participants: Sixty-four glaucoma subjects with bilateral visual field (VF) loss and 59 glaucoma suspects with normal VFs., Methods: Consecutive patients were recruited prospectively from the Wilmer Eye Institute Glaucoma Clinic., Main Outcome Measures: Tear film breakup time (TBUT), corneal staining score (0-15), and Schirmer's test results were included as objective metrics, whereas the Ocular Surface Disease Index (OSDI) questionnaire was administered to assess symptoms. Total OSDI score, vision-related subscore (derived from questions about vision and task performance), and discomfort-related subscore (derived from questions about ocular surface discomfort) were calculated for each subject., Results: Seventy-five percent (48/64) of glaucoma subjects and 41% (24/59) of glaucoma suspects were receiving topical medications. The corneal staining grade was greater in glaucoma subjects than in glaucoma suspects (6.4 vs. 4.1; P<0.001), but groups did not differ with regard to TBUT or Schirmer's results (P>0.20 for both). Multivariate regression models showed that topical glaucoma therapy burden was associated with a significantly higher total corneal staining grade (β, +0.9 for each additional glaucoma drop; 95% confidence interval [CI], 0.5-1.3; P<0.001), but not with TBUT or Schirmer's results (P>0.20 for both). Glaucoma subjects had significantly higher total OSDI scores than glaucoma suspects (16.7 vs. 7.9; P<0.001). This largely was the result of higher vision-related subscores in the glaucoma group (11.1 vs. 3.3; P<0.001). Ocular discomfort-related subscores, however, were similar in both groups (5.7 vs. 4.6; P = 0.30). In multivariate analyses, each 5-decibel decrement in better-eye VF mean deviation was associated with a 4.7-point increase in total OSDI score (95% CI, 1.9-7.5; P = 0.001) and a 3.7-point increase in the vision-related subscore (95% CI, 1.7-5.6; P<0.001) but did not predict a higher discomfort-related subscore (β, 1.1 point; P = 0.07). Topical glaucoma therapy burden was not associated with higher total OSDI score or vision- or discomfort-related subscore (P>0.20 for all)., Conclusions: Glaucoma is associated with significant ocular surface disease, and topical glaucoma therapy burden seems predictive of corneal staining severity. However, OSDI is a poor metric for capturing ocular surface disease in glaucoma because symptoms seem to be related largely to VF loss., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background and Objective: To evaluate femtosecond laser-created tunnels intraoperatively by anterior segment optical coherence tomography (AS-OCT) during intrastromal corneal ring segment implantation., Patients and Methods: The study prospectively examined 13 eyes of 11 patients who underwent intrastromal corneal ring segment surgery with the aid of femtosecond laser. All eyes had keratoconus as the primary diagnosis. Eyes were examined by AS-OCT to image the tunnel immediately after femtosecond laser and before ring segment implantation. Tunnel depth was calculated automatically using the software's flap tool and calipers., Results: The presence of air bubbles demonstrated the tunnel successfully by AS-OCT. Tunnel depth was measured at eight locations in four cross-sections of high-resolution cornea images. An overall evaluation was also made by changing the scan direction 360°. After confirmation that a uniform tunnel was satisfactorily created at the aimed depth, surgery proceeded with segment implantation., Conclusion: AS-OCT can be used intraoperatively to assess femtosecond laser-created tunnel in intrastromal corneal ring segment implantation. The qualitative and quantitative evaluation of the intrastromal tunnel by AS-OCT before implantation of the ring segments is a practical intraoperative approach that may offer a safer surgery., (Copyright 2012, SLACK Incorporated.)

Purpose: To report the occurrence of chronic hypotony as a complication following Boston type 1 keratoprosthesis (KPro) implantation and to determine associated risk factors., Design: Retrospective case series., Methods: The medical records of all patients undergoing KPro implantation between January 2004 and November 2010 at the Wilmer Eye Institute were reviewed. Patients who developed chronic hypotony following Boston type 1 KPro implantation not attributable to anatomic problems (eg, retinal detachment, overfiltering glaucoma tube shunts, tissue necrosis with aqueous leak) or other causes were identified. Demographics and preoperative, intraoperative, and postoperative clinical findings were analyzed. Light microscopic examination of an enucleated globe as well as fibrous retroprosthetic membranes excised at the time of vitrectomy from another patient was performed., Results: Sixty-eight eyes received KPro implantation over the study period. Six eyes experienced chronic hypotony, with a median time of 18.5 months between KPro implantation and the onset of hypotony. The incidence of chronic hypotony in this series was calculated to be 3.7% at 1 year (95% CI = 0.9%-14.0%) and 13.3% at 2 years (95% CI = 5.5%-30.0%). Of the 6 eyes that developed chronic hypotony, 5 had a previous history of glaucoma or ocular hypertension, but only 3 had a glaucoma drainage implant. All eyes progressing to chronic hypotony were noted to have a retroprosthetic membrane prior to the onset of hypotony. Cox regression modeling demonstrated an increased risk of chronic hypotony in eyes with retroprosthetic membranes (P < .01) but no increase in risk for older patients (P > .1), eyes with glaucoma drainage implants (P > .5), or a previous history of multiple donor corneal transplants (P > .5)., Conclusion: Chronic hypotony can be a significant complication of KPro implantation and should be assessed carefully in eyes with retroprosthetic membranes. Further study of an association between hypotony and retroprosthetic membrane formation may be useful to gain insight into the mechanism of this complication and potential prevention or treatment options., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the long-term effectiveness of the combination of topical cyclosporine drops and tacrolimus ointment in the treatment of steroid-dependent atopic keratoconjunctivitis (AKC)., Methods: Ten patients with moderate to severe AKC participated in the study. Topical cyclosporine 0.05% was used, as a monotherapy, 6 times daily during the first month of the study, followed by 4 times daily during the second month. The patients were then instructed to self-treat with topical cyclosporine at a dose ranging from 2 to 6 times daily depending on the severity of the disease. Tacrolimus ointment 0.03% was applied on the lid skin. Follow-up examinations were performed approximately every 3 months. Each patient completed a follow-up period of at least 12 months. Symptoms and signs of AKC were assessed on the day of enrollment, on days 28, 56, and 63, and at subsequent follow-up visits. Flare-ups of AKC requiring steroid use and progression of the disease findings were also recorded., Results: All patients experienced significant improvement of their symptoms and signs during the first 2 months of the study. Two patients were lost to follow-up after the initial 2 months. One patient was noncompliant and continued the treatment only for 7 months. During the median treatment period of 21.5 months for the 7 continuing patients, a total of only 2 flare-up episodes were noted requiring topical steroids., Conclusions: Adequate topical immunomodulation using topical calcineurin inhibitors may eliminate the need for steroids and favorably alter the long-term prognosis of patients with AKC.

Purpose: To analyze the visual and refractive outcomes of laser in situ keratomileusis (LASIK) after deep anterior lamellar keratoplasty (DALK) for keratoconus., Setting: Haydarpasa Numune Education and Research Hospital, Ophthalmology Clinic, Istanbul, Turkey., Design: Cohort study., Methods: Patients with compound myopic astigmatism after DALK and a spherical equivalent (SE) between -2.50 diopters (D) and -8.00 D had LASIK as a single-step procedure, correcting the manifest refraction error. The visual and refractive results at 1 month, 3 months, and the last follow-up were compared with preoperative values., Results: The mean follow-up was 11.17 months ± 3.61 (SD). The mean manifest refraction SE (MRSE) and autorefractometer measurements and the autokeratorefractometer and corneal topography keratometry readings decreased significantly from preoperatively to 1 month postoperatively (P<.01) but did not change significantly thereafter (P>.05). Preoperatively, the mean uncorrected (UDVA) and corrected (CDVA) distance visual acuities were 0.21 ± 0.08 and 0.73 ± 0.08, respectively; postoperatively, the means were 0.73 ± 0.10 and 0.98 ± 0.05, respectively. All eyes achieved a postoperative UDVA better than 0.5. No eye lost CDVA lines. The safety index was 1.34. The mean MRSE was -5.18 ± 1.74 D preoperatively and -1.05 ± 0.64 D postoperatively (P<.01). Postoperatively, 11 eyes (91.67%) were within ± 2.00 D of the SE, 8 (6.67%) were within ± 1.00 D, and 5 (41.67%) were within ± 0.50 D. No complications were encountered., Conclusion: Treatment of post-DALK keratoconus patients with LASIK to correct manifest refraction error seems to be a viable option., (Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To monitor corneal thickness during the corneal collagen cross-linking procedure in corneal ectatic diseases, by using isoosmolar riboflavin solution with 20% dextran and hypoosmolar riboflavin solution without dextran., Methods: The corneal thickness measurements were obtained at 5 different time points: after epithelial removal, after isotonic riboflavin solution application for 30 minutes, after hypotonic riboflavin solution application for 10 minutes, and after 10 and 30 minutes of isotonic riboflavin solution application., Results: A total of 9 eyes of 9 patients with progressive keratoconus (n = 8) and pellucid marginal degeneration (n = 1) were included in this study. After epithelial debridement, the thinnest pachymetric readings were between 331 and 399 μm (average, 376.11 ± 19.88 μm). The thinnest pachymetric measurements decreased significantly after the application of isoosmolar riboflavin solution for 30 minutes (by 55.22 ± 13.40 μm) and increased significantly after hypoosmolar riboflavin application for 10 minutes (by 59.56 ± 29.71 μm) (P < 0.01 for both). This artificial swelling effect was transient, and the thinnest pachymetric readings decreased significantly after 10 and 30 minutes of isoosmolar riboflavin application compared with thickness at the end of hypoosmolar riboflavin application (by 50.22 ± 29.68 μm and 65.11 ± 27.94 μm, respectively) (P < 0.01 for both)., Conclusions: The iatrogenic swelling effect of the hypoosmolar riboflavin solution might be short acting and not durable throughout the UVA application in collagen cross-linking procedure.

Purpose: To evaluate the refractive, topographic, optical, visual acuity, and quality outcomes of two types of intrastromal corneal ring segments (ICRS) in the treatment of keratoconus., Methods: In this retrospective study, 16 eyes that had been implanted with Intacs ICRS (Addition Technology Inc) (Intacs group) and 17 eyes implanted with Ferrara ICRS (Ferrara Ophthalmics Ltda) (Ferrara group) were evaluated. Pre- and postoperative examinations included uncorrected and corrected distance visual acuities (UDVA and CDVA, respectively), manifest refraction, slit-lamp examination, topography, and ocular wavefront analysis. Contrast sensitivity measurements under photopic, scotopic, and scotopic with glare conditions were performed 1 year postoperatively., Results: One year postoperatively, a significant decrease was noted in spherical equivalent refractive error of 3.76 ± 0.39 diopters (D) and 3.42 ± 0.88 D and keratometry of 3.43 ± 0.24 D and 3.28 ± 0.78 D in the Intacs and Ferrara groups, respectively; and increase in mean UDVA and CDVA in Snellen lines of 0.18 ± 0.04 and 0.21 ± 0.05, respectively, in the Intacs group and 0.21 ± 0.09 and 0.26 ± 0.08, respectively, in the Ferrara group (P<.01 for all). The postoperative increase in UDVA and CDVA and decrease in keratometry readings were not significantly different between groups (P>.05 for all). Mean higher order aberrations decreased in the Intacs group and increased in the Ferrara group (P>.05 for both). Postoperatively, a significant decrease was noted in scotopic contrast sensitivity when glare was introduced in the Ferrara group, which was positively correlated with pupil diameter (r(15)=0.50, P=.04)., Conclusions: Both ICRS types provided comparable refractive, topographic, and optical quality outcomes. Eyes with Ferrara ICRS experienced greater decrease in scotopic contrast sensitivity under glare, which was significantly correlated with pupil diameter.

Purpose: To compare phacoemulsification-related endothelial cell loss in eyes with previous penetrating keratoplasty (PKP), previous deep anterior lamellar keratoplasty (DALK), or no previous corneal surgery., Setting: Ophthalmology Clinic, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey., Design: Comparative case series., Methods: Eyes with previous PKP (Group 1), previous DALK (Group 2), or no previous ocular surgery (Group 3) had extracapsular cataract extraction by phacoemulsification. The endothelial cell count was evaluated 1, 3, 6, and 12 months after cataract surgery., Results: Group 1 comprised 16 eyes and Group 2 and Group 3, 20 eyes each. The endothelial cell density (ECD) decreased progressively throughout the follow-up in all groups (P<.01). The amount of change in ECD was significantly greater in Group 1 than in Group 2 and Group 3 from preoperatively to 1 month postoperatively, from 1 to 3 months postoperatively, from 3 to 6 months postoperatively, and from 6 to 12 months postoperatively (all P<.01). The changes were similar in Group 2 and Group 3 at all time points (P>.05)., Conclusions: Eyes with previous PKP had significantly greater endothelial cell loss than eyes with previous DALK or no previous surgery. Preservation of the patient's endothelium seems to be an advantage of DALK in terms of increasing corneal safety in future intraocular surgery., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the short-term visual and clinical outcomes of explantation versus preservation of a posterior chamber intraocular lens (PC IOL) during keratoprosthesis implantation., Setting: Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA., Design: Comparative case series., Methods: This study comprised patients who had implantation of an aphakic or a pseudophakic Boston type I keratoprosthesis based on their lenticular status. Only adult patients who were pseudophakic with a PC IOL at the time of surgery and who had at least 1 year of follow-up were included. The postoperative refractive error, uncorrected and corrected visual acuities, and intraoperative and postoperative complications were analyzed., Results: Fifteen patients with an unstable PC IOL had aphakic keratoprosthesis implantation with IOL explantation, and 10 patients had implantation of a pseudophakic keratoprosthesis. The postoperative best-ever visual acuity and magnitude of visual acuity improvement were comparable in the 2 groups. The mean postoperative spherical equivalent refractive error was significantly better in the aphakic group (-0.66 diopter [D] ± 1.59 [SD]) than in the pseudophakic group (-3.25 ± 3.20 D) (P=.04). The rate of postoperative complications in the 2 groups was low (P>.05)., Conclusions: In this small short-term study, refractive outcomes were better in aphakic patients than in patients who were left pseudophakic. Although not frequent, posterior segment complications after IOL explantation might necessitate further surgeries and cause decreased visual acuity during long-term follow-up in the aphakic group., (Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Background: To evaluate the tear osmolarity in patients with dry eye syndrome related to primary Sjögren's Syndrome (SS)., Materials and Methods: Twenty eyes of 10 patients with dry eye and primary SS (Group 1) and 20 eyes of 20 subjects who do not have dry eye syndrome (Group 2) were included in this cross-sectional study. In all eyes, ophthalmic examination was performed in the same order: International Ocular Surface Disease Index survey, visual acuity assessment, conjunctival hyperemia scoring, tear osmolarity measurement with TearLab(™) Osmolarity System, tear film break-up time assessment, corneal fluorescein staining scoring, ocular surface Lissamine Green staining scoring, anesthetized Schirmer test. Dry eye severity was graded according to Dry Eye Workshop (DEWS) classification system., Results: Four eyes with grade 1, four eyes with grade 2, seven eyes with grade 3, and five eyes with grade 4 dryness, according to DEWS system, were included. The mean tear osmolarity value was 301.9 ± 11.40 mOsm/L (range: 290-328) in Group 1, and 294.85 ± 8.33 mOsm/L (range: 283-311) in Group 2 (p = 0.03). In Group 1, tear osmolarity values were positively correlated with OSDI scores (r(18) = 0.55, r(2) = 0.31, p = 0.01), DEWS classification grades (r(18) = 0.73, r(2) = 0.54, p < 0.01), temporal and total corneal staining scores (r(18) = 0.67, r(2) = 0.44, p < 0.01, and r(18) = 0.51, r(2) = 0.26, p = 0.02, respectively), temporal conjunctival staining scores (r(18) = 58, r(2) = 0.34, p < 0.01); and negatively correlated with anesthetized Schirmer test results (r(18) = -0.62, r(2) = 0.38, p < 0.01) and TFBUT (r(18) = -0.50, r(2) = 0.25, p = 0.02)., Conclusions: Tear osmolarity values were found to be greater in patients with dry eye syndrome related to primary SS compared to control subjects, and positively correlated with the severity of dry eye.

Purpose: To examine the corneal collagen cross-linking (CXL) effect with a customized epithelial debridement technique in thin corneas using anterior segment optical coherence tomography (OCT) and confocal microscopy., Methods: Two patients with keratoconus who underwent a customized epithelial debridement technique (preserving the epithelium in thinner corneal regions where the deepithelialized corneal thickness was <400 μm) and subsequent CXL were examined by anterior segment OCT and in vivo confocal microscopy 1 month postoperatively., Results: Anterior segment OCT showed the demarcation line in the peripheral deepithelialized corneal areas, but it was not detectable in the central corneal regions corresponding to the cone where the epithelium was preserved. In vivo confocal microscopy analysis revealed total loss of keratocytes together with the intense honeycomb-like stromal edema in the anterior ∼320 μm of the cornea in the deepithelialized areas. This effect was mild under the intact epithelium with preservation of keratocytes and only a mild increase in stromal reflectivity., Conclusions: In this confocal microscopy study, the corneal stroma under the intact epithelium seemed to be spared from the collagen CXL effect by the customized epithelial debridement technique., (Copyright 2011, SLACK Incorporated.)