Current methodology and cell sources for lacrimal gland tissue engineering.

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.

Wide-field vitreoretinal surgery in eyes with Boston type 1 keratoprosthesis.

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.

Common ocular findings in patients with acne rosacea.

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.

Ahmed glaucoma valve implantation with the tube placement in the ciliary sulcus: short-term results.

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.

TNF-α Inhibitors for the Management of Intractable Corneal Melt: Report of Three Cases and Review of the Literature.

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.

Management of Reverse Pellucid Type Topography.

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.

Effects of Preoperative Topometric Indices on Visual Gain After Intracorneal Ring Segment Implantation For Keratoconus.

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.

Topically applied 1% voriconazole induces dysplastic changes on the ocular surface: animal study.

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.

Can the effect of transepithelial corneal collagen cross-linking be improved by increasing the duration of topical riboflavin application? An in vivo confocal microscopy study.

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.

Tissue Engineering and Ophthalmology.

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.

Generation of Anterior Segment of the Eye Cells from hiPSCs in Microfluidic Platforms.

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.

Management of glaucoma with Boston type 1 keratoprosthesis.

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.

Optical Coherence Tomography Angiography Imaging of Foveal Atrophy Secondary to Commotio Retinae in a Pediatric Patient.

Optical coherence tomography-angiography (OCTA) is a fast, reliable, and non-invasive technique for the diagnosis and follow-up of patients with commotio retinae (CR). Severity of the damage to the retinal and choroidal microvasculature in OCTA imaging and the visual prognosis are directly related to the severity of trauma. There are a few published reports on OCTA in CR that shows alterations of the retinal or superficial choroidal vessels and choriocapillary plexus. OCTA imaging seems to be predictive for visual prognosis. Herein, we present a 6-year-old boy, who had blunt trauma to the right eye with a stick during outdoor playing with visual acuity reduction to 0.1 following resolution of the Berlin's edema. In our case, OCTA revealed damage to the outer layers of the retinae and choriocapillaris and resulting in permanent vision loss. OCTA is a non-invasive, rapid, and safe imaging technique that qualitatively and quantitatively analyzes blood flow from the superficial capillary plexus to the choriocapillaris, which can be predictive in the visual prognosis.

Management of Suprachoroidal Hemorrhage during Cataract Surgery: A Case Report.

A 61-year-old patient with end-stage liver cirrhosis was admitted for cataract surgery with corrected distance visual acuities (CDVAs) of 0.3, in both eyes. His international correction ratio (INR) for blood coagulation was 2.1 without any anticoagulants, and general anesthesia was contraindicated. He was deemed inoperable for liver transplantation. Two weeks after uneventful phacoemulsification in his right eye under topical anesthesia, he underwent phacoemulsification for the cataract in the left eye. However, during surgery, extensive zonular dialysis was noted and the surgery proceeded with extracapsular cataract extraction and anterior vitrectomy, during which a rapid suprachoroidal hemorrhage (SCH) was noted. The incisions were then rapidly sutured. Intravenous 150 cc of 18% mannitol and 2 mg midazolam and sublingual 5 drops of nifedipine were given, and he was placed in the slightly reverse-trendelenburg position. Following suturation of the incision, the globe was left aphakic, slightly hypertonic with no loss of vitreous through the incisions. The postoperative treatment regimen of topical prednisolone and moxifloxacin eye drops of each per hour, cyclopentolate three times a day, and peroral prednisolone 40 mg was commenced. Despite no retinal reflex on the first day and no light perception for 2 weeks, transscleral SCH evacuation with limited pars plana vitrectomy was performed in the postoperative third week. Despite recurrent hemorrhage and intravitreal inflammatory bands, choroidal detachments regressed slowly with the improvement of CDVA up to 0.6 with aphakic contact lens correction at 3 months. The patient passed away due to complications of liver cirrhosis at 6 months.

Development of lacrimal gland organoids from iPSC derived multizonal ocular cells.

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 ß-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.

Efficacy of corneal collagen cross-linking using a custom epithelial debridement technique in thin corneas: a confocal microscopy study.

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.

Refractive and visual outcomes after Intacs vs ferrara intrastromal corneal ring segment implantation for keratoconus: a comparative study.

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.

Ocular surface disease associated with dupilumab treatment for atopic diseases.

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.

The number of intracorneal ring segments in asymmetric and central cones.

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.

Survival of penetrating keratoplasty: a claims-based longitudinal analysis.

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.