Outcomes of 320-degree intrastromal corneal ring segment implantation for advanced keratoconus.

PURPOSE: The purpose of this study is to investigate visual and tomographic outcomes and complications of long-arc length intrastromal corneal ring segment (ICRS) implantation for the treatment of advanced keratoconus. MATERIALS AND METHODS: This retrospective study enrolled 10 eyes of 9 subjects. All patients received 320-degree ICRS (320-ICRS) implantation with femtosecond laser-assisted technique based on their advanced grading with preoperative high keratometry (K) value, asphericity (Q), and astigmatism. Medical records and corneal tomography changes of consecutive patients were reviewed at baseline, 1, and 3 months after treatment. RESULTS: There are 6 female and 3 male patients with a mean age of 29.6 ± 7.8 years in this study. Mean K (Km) reduced from 59.01 ± 5.81 D preoperatively to 50.7 ± 5.3 and 50.2 ± 3.66 postoperatively (after 1 month and 3 months respectively, P < 0.001). The changes in mean K, K1, K2, and maximum K (Kmax) reading were all statistically significant (all P < 0.001). Mean uncorrected distance visual acuity (UCVA) improved from 20/400 to 20/200. Mean best-corrected distance visual acuity (BCVA) improved from 20/100 to 20/60. Both UCVA and BCVA showed a trend of improvement at postoperative month 3, though insignificant in BCVA (P = 0.114). Mean Q improved from -1.59 ± 0.62 preoperatively to -0.48 ± 1.08 and -0.11 ± 1.04 postoperatively (after 1 month and 3 months respectively, P = 0.016, 0.002). No intraoperative or postoperative complications were observed. CONCLUSIONS: The present results suggest that implanting a 320-ICRS is a safe and effective procedure for treating patients with advanced keratoconus. Preoperative corneal measurements and the selection of types and thickness of ICRS are important to prevent unpredictable results.

Bilateral keratitis associated with afatinib therapy.

This case discussed a significant ocular side effect, bilateral keratitis, which could be induced by afatinib, an irreversible epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). We explored the disease progression of a 52-year-old, stage IV nasopharyngeal carcinoma male patient, who was under afatinib treatment and had experienced progressive bilateral eye dryness and tenderness on increasing afatinib from 40 mg every other day to 40 mg daily. Clinical examination noted bilateral visual acuity reduction, diffuse superficial punctate keratopathy in the right eye, and a central epithelial defect in the left eye. Seidel test results were negative for both eyes, with no corneal infiltration, lagophthalmos, anterior chamber cell precipitation, or retinal lesion. Symptoms subsequently resolved after reducing the frequency of afatinib used, along with intensive ocular hydration. In summary, this case highlighted afatinib's potential link to bilateral keratitis, and early afatinib dose adjustment with supportive medication could significantly reverse the condition.

Targeting Ca2+-dependent pathways to promote corneal epithelial wound healing induced by CISD2 deficiency.

Chronic epithelial defects of the cornea, which are usually associated with severe dry eye disease, diabetes mellitus, chemical injuries or neurotrophic keratitis, as well as aging, are an unmet clinical need. CDGSH Iron Sulfur Domain 2 (CISD2) is the causative gene for Wolfram syndrome 2 (WFS2; MIM 604928). CISD2 protein is significantly decreased in the corneal epithelium of patients with various corneal epithelial diseases. Here we summarize the most updated publications and discuss the central role of CISD2 in corneal repair, as well as providing new results describing how targeting Ca2+-dependent pathways can improve corneal epithelial regeneration. This review mainly focuses on the following topics. Firstly, an overview of the cornea and of corneal epithelial wound healing. The key players involved in this process, such as Ca2+, various growth factors/cytokines, extracellular matrix remodeling, focal adhesions and proteinases, are briefly discussed. Secondly, it is well known that CISD2 plays an essential role in corneal epithelial regeneration via the maintenance of intracellular Ca2+ homeostasis. CISD2 deficiency dysregulates cytosolic Ca2+, impairs cell proliferation and migration, decreases mitochondrial function and increases oxidative stress. As a consequence, these abnormalities bring about poor epithelial wound healing and this, in turn, will lead to persistent corneal regeneration and limbal progenitor cell exhaustion. Thirdly, CISD2 deficiency induces three distinct Ca2+-dependent pathways, namely the calcineurin, CaMKII and PKCα signaling pathways. Intriguingly, inhibition of each of the Ca2+-dependent pathways seems to reverse cytosolic Ca2+ dysregulation and restore cell migration during corneal wound healing. Notably, cyclosporin, an inhibitor of calcineurin, appears to have a dual effect on both inflammatory and corneal epithelial cells. Finally, corneal transcriptomic analyses have revealed that there are six major functional groupings of differential expression genes when CISD2 deficiency is present: (1) inflammation and cell death; (2) cell proliferation, migration and differentiation; (3) cell adhesion, junction and interaction; (4) Ca2+ homeostasis; (5) wound healing and extracellular matrix; and (6) oxidative stress and aging. This review highlights the importance of CISD2 in corneal epithelial regeneration and identifies the potential of repurposing venerable FDA-approved drugs that target Ca2+-dependent pathways for new uses, namely treating chronic epithelial defects of the cornea.

Functional and Anatomical Outcomes of Anti-Vascular Endothelial Growth Factor Treatment for Exudative Age-Related Macular Degeneration with or without Obstructive Sleep Apnea.

(1) To investigate the functional and anatomical outcomes of anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with exudative age-related macular degeneration (AMD) with or without obstructive sleep apnea (OSA); (2) In total, 65 patients with AMD with or without OSA who received three consecutive doses of intravitreal anti-VEGF injections were enrolled. The primary outcomes-best-corrected visual acuity (BCVA) and central macular thickness (CMT)-were assessed at 1 and 3 months. Moreover, morphological changes observed through optical coherence tomography were analyzed; (3) In total, 15 of the 65 patients had OSA and were included in the OSA group; the remaining 50 patients were included in the non-OSA (control) group. At 1 and 3 months after treatment, BCVA and CMT had improved but did not differ significantly between the groups. More patients in the OSA group demonstrated subretinal fluid (SRF) resorption at 3 months after treatment than in the non-OSA group (p = 0.009). Changes in other imaging biomarkers, such as intraretinal cysts, retinal pigment epithelium detachment, hyperreflective dots, and ellipsoid zone disruptions, did not differ significantly between the groups; (4) Our results suggest that the BCVA and CMT outcomes 3 months after anti-VEGF treatment are similar between patients with and without OSA. Moreover, patients with OSA may exhibit superior SRF resorption. A large-scale prospective study is mandatory to evaluate the association between SRF resorption and visual outcomes in AMD patients with OSA.

Change of Optical Coherence Tomography Morphology and Associated Structural Outcome in Diabetic Macular Edema after Ranibizumab Treatment.

(1) Background: To investigate the correlation between therapeutic outcome and morphologic changes for diabetic macular edema (DME) after intravitreal injection of ranibizumab (IVIR). (2) Methods: This retrospective study included 228 eyes received IVIR for DME. Each participant was traced for two years after the initial IVIR, while the data of ophthalmic examination, optical coherence tomography (OCT) image, and systemic diseases were collected. The study population was categorized into different subgroups according to the existence of OCT morphologic change and the initial OCT morphologic pattern, including diffuse retinal thickening (DRT), cystoid macular edema (CME), serous retinal detachment (SRD), and vitreomacular interface abnormalities (VMIAs). The primary outcomes were the baseline best-corrected visual acuity (BCVA) and central macular thickness (CMT) during a two-year study period. The distribution of OCT morphologic change and its relation to primary outcome were analyzed. (3) Results: Comparing the 42 eyes (18.4%) with OCT morphological changes to another 186 eyes (81.6%) without such alteration, the former showed a poorer baseline BCVA (0.84 ± 0.39 vs. 0.71 ± 0.36, p = 0.035), worse final BCVA (0.99 ± 0.44 vs. 0.67 ± 0.30, p = 0.001), and thicker final CMT (354.21 ± 89.02 vs. 305.33 ± 83.05, p = 0.001). Moreover, the VMIA developed in 14.9% of all DME patients presenting the most common morphologic change among DRT, CME, and SRD. Besides, the presence of stroke was independently correlated to the morphologic change (adjusted odds ratio [aOR]: 6.381, 95% confidence interval (CI): 1.112-36.623, p = 0.038). (4) Conclusions: The change of OCT morphology in DME patients receiving IVIR was correlated to worse structural and visual outcome while the formation of VMIA most commonly occurred after initial treatment.

Optical coherence tomography and imaging biomarkers as outcome predictors in diabetic macular edema treated with dexamethasone implant.

In this retrospective, multicenter study, we determined the predictive value of imaging biomarkers in diabetic macular edema (DME) outcomes following dexamethasone (DEX) implant(s). Sixty-seven eyes of 47 patients' best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography (OCT) before and after intravitreal DEX implants were evaluated. Baseline imaging biomarkers were graded using fundus photography and OCT, and the predictive value of biomarkers for significant treatment effects at six months was analyzed. Six months after 2.0 ± 0.8 (mean ± SD) DEX implants, 35 (52%) and 16 (24%) eyes had CFT reduction ≥ 10% from baseline and decreased to < 300 µm, respectively. BCVA improved ≥ 3 lines in 15 (22%) and remained stable in 38 (57%) eyes. At six months, eyes with severe intraretinal cyst (IRC), abundant hyperreflective dots (HRD), and moderate or severe hard exudate had a significantly higher chance of CFT reduction ≥ 10%. Eyes with abundant HRD at baseline and those underwent three DEX implants were more likely to achieve CFT < 300 µm. Eyes with DME and severe IRC, abundant HRD, or moderate-to-severe hard exudate at baseline were more likely to show a significant reduction in CFT six months after DEX implant.

Post-operative optical coherence tomography angiography features of chorioretinal folds resulting from pleomorphic adenoma of the lacrimal gland (PALG) of orbit- a case report.

BACKGROUND: Chorioretinal fold (CFs) is a rare condition resulting from undulations in the choriocapillaris, Bruch's membrane, retinal pigment epithelium and occasionally neurosensory retina. It can be idiopathic or due to different etiologies. The use of spectral-domain optical coherence tomography (SD-OCT) has increased the diagnosis of CFs and helped in differentiation from other etiologies. Recently, optical coherence tomography angiography (OCT-A) emerged as a non-invasive imaging technique allowing visualization of the individual layers of microvasculature of the retina and the choroid by comparing consecutive B-scans. We described a rare case of pleomorphic adenoma of the lacrimal gland (PALG) causing hyperopic shift and CFs with the new OCT-A technology, getting deeper insight into vascular changes of this disease. CASE PRESENTATION: A 40-year-old Asian man experienced progressive blurred vision in his right eye over 6 months. The patient's initial axial lengths were 25.55 mm in the right eye and 28.13 mm in the left eye. Fundus examination in the right eye revealed oblique CFs as well as the SD-OCT displayed. Magnetic resonance imaging showed intraconal mass extended from superior temporal side of the right orbit. The patient then received tumor removal surgery through lateral orbitotomy and histopathology confirmed a pleomorphic adenoma of the orbit. The patient had regular follow-up for 1 year. His best corrected visual acuity markedly improved from 20/50 to 20/20 with nearly stationary AXL. We performed OCT-A at one year after the surgery, which showed early visualization of deep choroidal vessels. The scleral remodeling due to mass effect of retrobulbar tumor also caused displacement of the deep large choroidal vessels over the superior macular area even after tumor removal. CONCLUSIONS: We reported a rare case of PALG with hyperopic shift and CFs as initial presentation. Surgical removal of the tumor partially resolved the CFs and contributes to impressive visual acuity recovery. The use of OCT-A provided a deeper insight to vascular architecture changes resulting from scleral remodeling after long-term tumor compression.

Optical Coherence Tomographic Patterns as Predictors of Structural Outcome After Intravitreal Ranibizumab in Diabetic Macula Edema.

BACKGROUND/OBJECTIVES: The purpose of this study was to present an association between the treatment response of diabetic macular edema (DME) to intravitreal ranibizumab (IVR) injections and different morphology patterns using spectral domain optical coherence tomography (SD-OCT). SUBJECTS/METHODS: This retrospective study included 216 eyes of 142 subjects who received IVR for DME and were observed for at least 2 years. Medical charts and SD-OCT images of consecutive patients were reviewed at baseline, 1, 3, 6, 12, and 24 months after first IVR treatment. The OCT patterns were characterized as diffuse retinal thickening (DRT), cystoid macular edema (CME), serous retinal detachment (SRD), and vitreomacular interface abnormalities (VMIAs). All patients were classified into four groups based on the OCT findings. RESULTS: For a total of 216 eyes, 36 eyes were classified into the DRT group, 76 in the CME group, 42 in the SRD group, and 62 in the VMIA group. There were significant central macula thickness (CMT) improvements in all groups at the 1st month and the 2nd year, except for the DRT group at the 2nd year. Patients with OCT findings of hyperreflective dots (HRDs), metabolic parameters of hyperlipidemia, and coronary artery disease (CAD) had significantly less improvements in CMT at 2-year follow-up (P=0.029, 0.007, <0.001, respectively). CONCLUSION: A trend toward decreased effectiveness after long-term IVR treatment was observed in the DRT group. Consistent IVR treatment could still achieve favorable improvement in the reduction of CMT in 2-year follow-up in the VMIA group. Different OCT patterns in DME may affect the therapeutic role of anti-VEGF agents and predict the structure outcome.

Prevalence of microbial contamination in donor corneas.

BACKGROUND/PURPOSE: Postoperative infection is the most disastrous complication of penetrating keratoplasty (PK). Corneoscleral rim culture provided information regarding subsequent infections. Our aims were to identify the incidence of microbial contamination in donor corneas and to report the recovery of bacteria with two culture methods, i.e., conventional culture media after aerobic/anaerobic cotton swabs and blood culture media (Fastidious Antibiotic Neutralization [FAN]). MATERIALS AND METHODS: A total of 118 patients underwent PK. Corneoscleral rim cultures were performed using aerobic/anaerobic culture cotton swabs (Transystem™, COPAN, Italia) with subsequent convention media and blood culture media (FAN bottle, BD BACTEC™, USA). The results of the different methods were reported and analyzed. RESULTS: Microorganisms were recovered from 24 in total 118 cases (20.3%, n = 118), 14 from blood culture media (FAN) (11.8%, n = 118), 9 from conventional culture media after aerobic/anaerobic cotton swabs (7.63%, n = 118), and 2 from fungus culture (1.69%, n = 118). The most commonly identified pathogen was coagulase-negative Staphylococcus (CoNS) (n = 13, 54.2%), and more isolates of CoNS and staphylococcus aureus were recovered from blood culture media (FAN) than those from conventional culture media after aerobic/anaerobic cotton swabs (13 vs. 4, P = 0.05). Conversely, more nonfermentative Gram-negative bacilli were recovered from conventional culture media after aerobic/anaerobic cotton swabs. None of the 24 cases with positive corneoscleral rim cultures reported ocular infection for the recipients in at least 6 months' follow-up. CONCLUSION: The conventional culture media after aerobic/anaerobic cotton swabs and blood culture media (FAN) did not yield identical isolates of bacteria. The blood culture media (FAN) could further yield Gram-positive bacteria in addition to those recovered from convention media. It seemed adding gentamicin and streptomycin could achieve bacteriostatic effect instead of the bactericidal effect. The administration of postoperative antibiotic in the recipient was suggested.

Resolution of Unilateral Dome-Shaped Macula With Serous Detachment After Treatment of Topical Carbonic Anhydrase Inhibitors.

Dome-shaped macula (DSM) is a morphological feature outlined through the use of optical coherence tomography and characterized by an inward or anterior deviation of the macula with respect to chorioretinal concavity. Currently, there is no validated therapy for serous retinal detachment secondary to DSM. The authors report a case of childhood unilateral DSM in a hyperopic eye with normal axial length that was complicated with subretinal fluid (SRF). Topical carbonic anhydrase inhibitors may be an acceptable and safer option for patients presented with nonresolving SRF associated with DSM. Further randomized controlled trials are necessary to confirm the efficacy of this therapeutic approach. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e218-e221.].