Ocular Graft Versus Host Disease Following Allogeneic Stem Cell Transplantation: A Review of Current Knowledge and Recommendations

Graft versus host disease (GVHD) is a common complication of allogeneic stem cell transplantation (allo-SCT). Ocular GVHD develops in approximately 40-60% of patients following allo-SCT and its most common clinical manifestations include keratoconjunctivitis sicca and cicatricial conjunctivitis. Ocular GVHD may lead to severe ocular surface disease, which can significantly diminish quality of life and restrict daily activities. It is thus important to monitor the condition closely since with timely diagnosis, irreversible damage can be avoided. The current review will focus on updated information regarding ocular GVHD

The Ocular Surface Chemical Burns

Ocular chemical burns are common and serious ocular emergencies that require immediate and intensive evaluation and care. The victims of such incidents are usually young, and therefore loss of vision and disfigurement could dramatically affect their lives. The clinical course can be divided into immediate, acute, early, and late reparative phases. The degree of limbal, corneal, and conjunctival involvement at the time of injury is critically associated with prognosis. The treatment starts with simple but vision saving steps and is continued with complicated surgical procedures later in the course of the disease. The goal of treatment is to restore the normal ocular surface anatomy and function. Limbal stem cell transplantation, amniotic membrane transplantation, and ultimately keratoprosthesis may be indicated depending on the patients’ needs

Corneal Mesenchymal Stromal Cells Are Directly Antiangiogenic via PEDF and sFLT-1

Purpose To evaluate the angiogenic properties of corneal derived mesenchymal stromal cells (Co-MSC). Methods: Co-MSCs were extracted from human cadaver, and wild-type (C57BL/6J) and SERPINF1−/− mice corneas. The MSC secretome was collected in a serum-free medium. Human umbilical vein endothelial cell (HUVEC) tube formation and fibrin gel bead assay (FIBA) sprout formation were used to assess the angiogenic properties of Co-MSC secretome. Complete corneal epithelial debridement was used to induce corneal neovascularization in wild-type mice. Co-MSCs embedded in fibrin gel was applied over the debrided cornea to evaluate the angiogenic effects of Co-MSCs in vivo. Immunoprecipitation was used to remove soluble fms-like tyrosine kinase-1 (sFLT-1) and pigment epithelium-derived factor (PEDF, SERPINF1 gene) from the Co-MSC secretome. Results: Co-MSC secretome significantly inhibited HUVECs tube and sprout formation. Co-MSCs from different donors consistently contained high levels of antiangiogenic factors including sFLT-1 and PEDF; and low levels of the angiogenic factor VEGF-A. In vivo, application of Co-MSCs to mouse corneas after injury prevented the development of corneal neovascularization. Removing PEDF or sFLT-1 from the secretome significantly diminished the antiangiogenic effects of Co-MSCs. Co-MSCs isolated from SERPINF1−/− mice had significantly reduced antiangiogenic effects compared to SERPINF1+/+ (wild-type) Co-MSCs. Conclusions: These results illustrate the direct antiangiogenic properties of Co-MSCs, the importance of sFLT-1 and PEDF, and their potential clinical application for preventing pathologic corneal neovascularization

Optical Correction of Aphakia in Children

There are several reasons for which the correction of aphakia differs between children and adults. First, a child′s eye is still growing during the first few years of life and during early childhood, the refractive elements of the eye undergo radical changes. Second, the immature visual system in young children puts them at risk of developing amblyopia if visual input is defocused or unequal between the two eyes. Third, the incidence of many complications, in which certain risks are acceptable in adults, is unacceptable in children. The optical correction of aphakia in children has changed dramatically however, accurate optical rehabilitation and postoperative supervision in pediatric cases is more difficult than adults. Treatment and optical rehabilitation in pediatric aphakic patients remains a challenge for ophthalmologists. The aim of this review is to cover issues regarding optical correction of pediatric aphakia in children; kinds of optical correction , indications, timing of intraocular lens (IOL) implantation, types of IOLs, site of implantation, IOL power calculations and selection, complications of IOL implantation in pediatric patients and finally to determine the preferred choice of optical correction. However treatment of pediatric aphakia is one step on the long road to visual rehabilitation, not the end of the journey

Effect of Timolol on Refractive Outcomes in Eyes With Myopic Regression After Laser In Situ Keratomileusis: A Prospective Randomized Clinical Trial

Purpose To compare the effects of timolol on refractive outcomes in eyes with myopic regression after laser in situ keratomileusis (LASIK) with a control-matched group. Design Prospective, randomized, parallel-controlled, double-masked clinical trial. A computer-generated randomization list based on random block permutation (length 4 to 8) was used for treatment allocation. Methods SETTING: Basir Eye Center, Tehran, Iran. PATIENT POPULATION: Of 124 eyes with myopic regression after LASIK using Technolas 217-Z, 45 eyes in each group were analyzed. INTERVENTION: Patients were randomly assigned into either Group 1, who received timolol 0.5% eye drops, or Group 2, who received artificial tears for 6 months. MAIN OUTCOME MEASURE: Spherical equivalent (SE) at 6 months posttreatment. Results In Group 1, SE improved from −1.48 ± 0.99 diopter (D) before treatment to −0.88 ± 0.91 D and −0.86 ± 0.93 D 6 months after treatment and 6 months after timolol discontinuation, respectively (P <.001). In Group 2, it was −1.57 ± 0.67 D, −1.83 ± 0.76 D, and −1.91 ± 0.70 D, respectively (P <.001). SE was significantly better in Group 1 6 months after treatment and 6 months after discontinuation of treatment (P <.001 for both comparisons). There was a 0.26 D decrease in SE improvement every 4 months after the surgery in the Group 1 (P <.001). Conclusions Timolol application is effective for the treatment of myopic regression after LASIK compared with control group. Its effects last for at least 6 months after its discontinuation

Intravitreal bevacizumab injection alone or combined with triamcinolone versus macular photocoagulation in bilateral diabetic macular edema; application of bivariate generalized linear mixed model with asymmetric random effects in a subgroup of a clinical trial

Purpose: To compare the efficacy of intravitreal bevacizumab (IVB) injection alone or with intravitreal triamcinolone acetonide (IVB/IVT) versus macular photocoagulation (MPC) in bilateral diabetic macular edema (DME). Methods: In this study we revisited data from a subset of subjects previously enrolled in a randomized clinical trial. The original study included 150 eyes randomized to three treatment arms: 1.25 mg IVB alone, combined injection of 1.25 mg IVB and 2 mg IVT, and focal or modified grid MPC. To eliminate the possible effects of systemic confounders, we selected fellow eyes of bilaterally treated subjects who had undergone different treatments; eventually 30 eyes of 15 patients were re-evaluated at baseline, 6, 12, 18, and 24 months. Using mixed model analysis, we compared the treatment protocols regarding visual acuity (VA) and central macular thickness (CMT). Results: Improvement in VA in the IVB group was significantly greater compared to MPC at months 6 and 12 (P = 0.037 and P = 0.035, respectively) but this difference did not persist thereafter up to 24 months. Other levels of VA were comparable at different follow-up intervals (all P > 0.05). The only significant difference in CMT was observed in favor of the IVB group as compared to IVB/IVT group at 24 months (P = 0.048). Conclusion: Overall VA was superior in IVB group as compared to MPC up to 12 months. Although the IVB group showed superiority regarding CMT reduction over 24 months as compared to IVB/IVT group, it was comparable to the MPC group through the same period of follow up

Region of Interest Densitometry Analysis of Descemet Membrane Endothelial Keratoplasty Dehiscence on Anterior Segment Optical Coherence Tomography

PurposeTo evaluate a region of interest (ROI) method of analyzing anterior segment optical coherence tomography (AS-OCT) corneal densitometry (CD) in the setting of Descemet membrane endothelial keratoplasty (DMEK) dehiscence.MethodsRetrospective chart review of eyes that underwent (1) DMEK for Fuchs dystrophy (2) between 2018 to 2020 with (3) a partial DMEK dehiscence on AS-OCT, (4) involvement of only one side of the graft, (5) high-quality corneal AS-OCT scan, and (6) location of dehiscence within the central 5.5 mm of the cornea. Image analysis of the ROIs with ImageJ compared the total edematous area, mean stromal CD, and ratio of anterior-to-posterior (A/P) stromal CD for regions of DMEK dehiscence compared to the contralateral side with an attached DMEK graft. Control regions (with no dehiscence) and postdehiscence resolution images were also analyzed.ResultsSeventy sectors of the 21 images from 21 eyes with DMEK dehiscence were included. Compared to the contralateral side, regions of DMEK dehiscence had larger total areas (P &lt; 0.0001), lower mean stromal CD (P = 0.0003), and higher A/P stromal CD (P &lt; 0.0001). All control regions and postdehiscence resolution images did not show any significant differences compared to the contralateral sides.ConclusionsThis technique to analyze multiple ROIs on AS-OCT can be useful to evaluate CD of specific regions of corneal pathology. Lower mean stromal CD and higher A/P stromal CD may specify corneal edema.Translational relevanceAnalyzing CD via multiple specific ROIs may be more suitable than measuring the CD of the full cornea and has broader applications extending to other corneal pathologies

Effects of Smoking on Optic Nerve Head Microvasculature Density in Glaucoma

PrcisDecreased superficial whole image capillary density was observed in open angle glaucoma (OAG) patients with high smoking intensity.PurposeTo investigate the effects of smoking on optic nerve head capillary density measured by optical coherence tomography angiography in patients with OAG.MethodsIn this retrospective cross-sectional study, perimetric and preperimetric glaucoma patients enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with optical coherence tomography angiography follow-up were included. Univariable and multivariable linear mixed analysis were performed to determine the effects of different variables on the superficial whole image capillary density.ResultsA total of 432 eyes of 271 glaucoma patients comprising 63 preperimetric (106 eyes) and 208 perimetric OAG (326 eyes) were included. A history of tobacco consumption was reported in 105 (38.8%). Among smokers, mean (95% confidence interval) smoking intensity was 12.8 (10.2, 15.5) pack-years. After adjusting for age, glaucoma severity and other confounders, each 10 pack-year increase in smoking intensity (95% confidence interval) was associated with -0.54 (-1.06, -0.02) % lower whole image capillary density ( P =0.041).ConclusionsSmoking intensity is associated with reduced optic nerve vessel density in glaucoma

Smoking Cessation May Reduce Risk of Visual Field Progression in Heavy Smokers

PrcisThe earlier a person quits smoking the more likely is the optic nerve be spared from damage.PurposeTo investigate the effect of smoking cessation on visual field (VF) progression in glaucoma.MethodsPrimary open angle glaucoma patients with a minimum of 3 years follow-up and 5 VFs were included. Linear mixed models were used to investigate the effects of smoking on the rates of 24-2 VF mean deviation loss after adjusting for confounding factors. Cox proportional hazard regression was used to identify whether different levels of smoking intensity were associated with VF progression with respect to different duration of quitting.ResultsFive hundred eleven eyes of 354 patients were included over the mean follow-up of 12.4 years. Mean baseline age (95% confidence interval) was 62.3 (61.2, 63.4) years. One hundred forty nine (42.1%) patients were smokers. In a multivariable model, smoking intensity was associated with faster VF loss (-0.06, 95% confidence interval (-0.10, -0.01) dB/year per 10 pack-years, P =0.01) among smokers. Heavy smokers (≥20 pack-years) who had quit ˂25 years prior had significantly greater odds of VF progression compared with never smokers (odds ratio=2.49 (1.01, 6.08); P =0.046). There was no significant difference in odds of VF progression in heavy smokers who had quit smoking more than 25 years compared with never smokers ( P =0.43). A significantly higher proportion of VF progression was found in heavy smokers who quit &lt; 25 years compared with heavy smokers who quit ≥25 years by Kaplan-Meier analysis ( P =&lt;0.001).ConclusionsAfter ≥25 years of smoking cessation, the risk of VF progression in former heavy smokers becomes similar to never smokers. Long-term smoking cessation may be associated with lower VF progression in glaucoma patients

Longitudinal Structure–Function Relationship&nbsp;between Macular Vessel Density and Thickness and Central Visual Field in Early&nbsp;Glaucoma

PurposeTo investigate the relationship of longitudinal changes in macular vessel density (VD) from OCT angiography and in ganglion cell complex (GCC) from OCT with central visual field (VF) in eyes with early glaucoma.DesignObservational cohort.ParticipantsA total of 95 eyes, 37 preperimetric and 58 with early glaucoma (24-2 VF mean deviation [MD] ≥&nbsp;-6 decibels), with an average follow-up of 3.8 years and 5.3 visits, were included.MethodsWhole-image VD (wiVD) and whole-image GCC (wiGCC) and parafoveal scans, as well as localized regions of interest (LROIs), hemiretinae of whole images, and superior, inferior, temporal, and nasal sectors of parafoveal maps, were matched with central VF locations. Age-adjusted rates of change of VD, GCC, mean sensitivity of VF locations, and 10-2 VF MD were calculated using linear mixed-effect models. Normalized rates of change were calculated for comparison of change rates in wiVD and wiGCC.Main outcome measuresStructure-function (SF) correlations of VD and GCC with central VF measurement change rates and comparison of different correlations of SF relationships after bootstrapping the difference of the correlation coefficients.ResultsVessel density loss and GCC thinning demonstrated significant correlations with central VF damage, globally and with most LROIs. The SF correlation (r, 95% confidence interval [CI]) between wiVD and 10-2 VF MD change rates was 0.42 [0.24, 0.58], whereas it was 0.27 [0.08, 0.45] between wiGCC and 10-2 VF MD changes rates (all P &lt; 0.05). In contrast to GCC thinning, VD loss in the parafoveal sectors demonstrated significant correlations with central VF damage in inferior and temporal sectors. Differences in the relationship of SF with central VF damage were not significant between VD loss and GCC thinning. The mean (95% CI) normalized change rates of wiVD (-7.40 [-7.71 to 7.09] %/year) was faster than that of wiGCC (-2.39 [-2.94 to 1.84] %/year) (P &lt; 0.05).ConclusionsRates of VD loss and GCC thinning are associated with central VF loss over time. Assessment of both macular VD and GCC thickness should be considered for evaluation of glaucoma progression