Effect of Topical Recombinant Human Nerve Growth Factor on Corneal Epithelial Regeneration in Refractory Epithelial Keratopathy.

PURPOSE: To report the effect of topical application of recombinant human nerve growth factor (rhNGF) eye drops on corneal epithelial regeneration in patients with refractory epitheliopathy. METHODS: A retrospective chart review was conducted on patients treated with topical rhNGF for refractory epithelial keratopathy due to stage I neurotrophic keratitis (NK). Data regarding demographics and ocular/systemic past medical history was extracted from patient charts. Visual acuity and corneal staining scores were recorded at baseline and subsequent follow-up visits at 8 weeks and 3 months. Measurements from the worse eye were used to compare before and after treatment values. RESULTS: We identified 14 patients (median age 68 years, 21% male) who received rhNGF treatment for refractory epithelial keratopathy. After an 8-week treatment with topical rhNGF, the median corneal staining score in the worse eye improved from 4 to 1 (p = 0.001). All patients showed at least one-grade improvement in corneal staining at 8 weeks, with sustained effect in seven patients at 3 months. A better response was observed in eyes with post-radiation epithelial keratopathy, LASIK, and Sjogren's disease. Those with chronic use of other topical treatments and uncontrolled diabetes mellitus demonstrated incomplete responses. Eight patients reported mild-to-moderate ocular discomfort from drop application that fully resolved after completion of treatment. CONCLUSIONS: Topical rhNGF was effective and safe for refractory epithelial keratopathy in our small cohort, but sustained effects were seen only in certain etiologies for up to 3 months. Further studies are needed for optimal dosing and duration based on underlying causes.

Assessment of Choroidal Vascularity in Inactive Thyroid Associated Orbitopathy.

Objectives: The objectives of the study were to evaluate the vascular and stromal structure of the choroid in patients with inactive thyroid associated orbitopathy (TAO) by measuring choroidal vascularity index (CVI) and choroidal thickness (CT) using enhanced depth imaging (EDI) optical coherence tomography (OCT). Methods: The choroidal image was taken with EDI mode spectral domain (SD)-OCT. All scans were taken between 9.30 am and 11.30 am to avoid the diurnal variation of CT and CVI. To calculate CVI, macular SD-OCT scans were binarized using the publicly available software ImageJ and luminal area and total choroidal area (TCA) were measured. CVI was calculated as the proportion of LA to TCA. Furthermore, the relation between CVI and axial length, gender, and age was evaluated. Results: This study included 78 individuals with a mean age of 51.4±7.3 years. Group 1 consisted of 44 patients with inactive stage TAO, and Group 2 consisted of 34 healthy controls. Subfoveal CT was 338.92±73.93 µm in Group 1 and 303.97±40.35 µm in Group 2 (p=0.174). The CVI significantly differed between the two groups, which was higher in group 1 (p=0.000). Conclusion: Although CT was not different between groups, CVI which is the indicator of the vascular status of the choroid, was higher in patients with TAO in the inactive stage compared with healthy control subjects.

Corneal bacterial microbiome in patients with keratoconus using next-generation sequencing-based 16S rRNA gene analysis.

PURPOSE: To investigate the corneal bacterial microbiome in patients with keratoconus using next-generation sequencing and develop a new perspective on the pathogenesis of the disease. METHODS: This prospective observational study included 10 patients with keratoconus who underwent corneal crosslinking procedure and 10 healthy controls who underwent photorefractive keratectomy. Patients included in the study were aged 18 years or older. The demographic and clinical characteristics of participants were recorded. Corneal epithelial samples were collected between March 2021 and June 2021. Isolated bacterial DNA from corneal epithelial samples was analyzed using 16 S ribosomal RNA gene analysis. The relative abundance rates at the phylum and genus levels were calculated. Alpha diversity parameters were assessed. RESULTS: Eleven phyla and 521 genera of bacteria were identified in all participants. At the phylum level, Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were most abundant in both groups. There were no statistical differences between the two groups except Bacteriodetes (p < 0.05). At the genus level, the relative abundance rates of twenty bacteria were significantly different between keratoconus and healthy corneas (p < 0.05). Aquabacterium was the most abundant genus in patients with keratoconus, while Shigella was the most abundant genus in healthy controls. Alpha diversity parameters were lower in patients with keratoconus, although the difference did not reach statistical significance (p > 0.05). CONCLUSIONS: Our preliminary study revealed that there are similarities and differences in the corneal microbiome between keratoconus and healthy individuals. Further research is required on the relationship between the abnormal corneal microbiome composition and the pathogenesis of keratoconus.

Comparison of topical omega-3 fatty acids with topical sodium hyaluronate after corneal crosslinking : Short term results.

PURPOSE: To evaluate the effect of topical omega 3 on ocular surface following corneal crosslinking (CXL) in keratoconus and compare with topical sodium hyaluronate. MATERIAL METHODS: 50 patients who underwent CXL were divided into two groups. In addition to topical steroids and antibiotics, Group A was prescribed topical omega 3; Group B was prescribed 0.3% sodium hyaluronate. Postoperatively, epithelial defect was measured everyday and at the first month corneal staining, Schirmer test was performed, tear break up time (TBUT), tear meniscus height (TMH) were measured. RESULTS: Preoperative keratometric values were similar between groups; there was no difference in terms of corneal staining, tear film stability; epithelial closure time (p: 0.052), and postoperative pain scores between groups. At 1st month, TBUT and TMH were significantly better in Group A than Group B(p: 0.001, p: 0.047). CONCLUSION: Topical omega 3 increases tear film stability more prominent than sodium hyaluronate following crosslinking.

Visual rehabilitation by using corneal wavefront-guided transepithelial photorefractive keratectomy for corneal opacities after epidemic keratoconjunctivitis.

PURPOSE: To evaluate long-term visual and refractive outcomes of corneal wavefront-guided transepithelial photorefractive keratectomy (t-PRK) with mitomycin C for the treatment of corneal opacities secondary to adenoviral epidemic keratoconjunctivitis. METHODS: Records of patients who underwent corneal wavefront-guided t-PRK with excimer laser from January 2012 to December 2018 were retrospectively reviewed. Preoperative and postoperative uncorrected visual acuity, best-spectacle corrected visual acuity, slit-lamp biomicroscopic examination findings, manifest refraction, and corneal aberrations and fundus examination findings were evaluated. RESULTS: Twenty-two eyes of 22 patients comprising 12 male (55%) and 10 female (45%) were treated. The mean age was 34.5 ± 10.8 years (range 19-55). The mean follow-up time was 34.4 ± 17.50 months (range 13-61 months). There was a statistically significant improvement in UCVA and BSCVA (p < 0.001 and p = 0.02), and there was a significant decrease in total higher-order aberrations, spherical, coma and trefoil aberration at postoperative first year (p < 0.001 in each). In two eyes of two patients, minimal haze formation was observed after the procedure, and both eyes were treated with topical steroid. No recurrence was observed in subepithelial infiltrates in any patient during long-term follow-up. CONCLUSION: In long-term clinical follow-up, corneal wavefront-guided t-PRK treatment is an effective and reliable treatment method for rehabilitation of visual impairment due to corneal scars following adenoviral infections, in properly selected patients.

Repeatability and reliability of measurements obtained by the combined Scheimpflug and Placido-disk tomography in different stages of keratoconus.

OBJECTIVE: The objective of this study is to evaluate the repeatability and reliability of corneal parameters in different stages of keratoconus patients using a combined Scheimpflug-Placido disc analysis system. MATERIALS AND METHODS: In this prospective study, three consecutive measurements were performed by the same observer using Scheimpflug-Placido disc anterior segment analysis device in keratoconus patients. Flattest and steepest simulated keratometry and corneal volume, corneal aberrations, thinnest corneal thickness, symmetry index, keratoconus vertex and Baiocchi-Calossi-Versaci index were recorded. Keratoconic eyes were divided into four stages using the Amsler-Krumeich classification. Repeatability was evaluated using within the subject standard deviation, repeatability index (Ri) and coefficient of variation; reliability was evaluated by intraclass correlation coefficient (ICC). Pearson correlation coefficients were used to assess the correlation between the parameters evaluated. RESULTS: Two hundred sixty-one eyes of 261 keratoconus patients were included in the study. The repeatability for all corneal curvature parameters decreased as the keratoconus severity increased, and there is a positive correlation between keratometry of the apex and corneal curvature parameters (p < 0.05) except mean simulated keratometry. The corneal aberrations were repeatable in all keratoconus subgroups (Ri < 0.34 µm). There are also positive correlations between keratometry of apex and corneal aberrations (p < 0.05) except total high-order root mean square and spherical aberration. The reliability was excellent (ICC > 0.90) for all indices except keratoconus vertex back. CONCLUSION: The parameters used in the diagnosis and follow-up of keratoconus in the Sirius corneal tomography system may differ more than expected at stages 3 and 4 of the disease. Awareness of this situation may be helpful in planning follow-up and treatment.

Correction: Choroidal vascularity index as an indicator of vascular status of choroid, in eyes with nanophthalmos.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Choroidal vascularity index as an indicator of vascular status of choroid, in eyes with nanophthalmos.

PURPOSE: To investigate choroidal vascular index (CVI) in eyes with nanophthalmos (NO) with the use of optical coherence tomography (OCT). METHODS: Macular enhanced depth imaging OCT scans of 25 eyes of 25 patients with NO and age-gender-matched 25 eyes of 25 control subjects were analysed. Images were binarized using the ImageJ software, and total choroid area (TCA), luminal area (LA) and stromal area (SA) were acquired. The main outcome measure was CVI, defined as the ratio of LA to TCA. RESULTS: Twenty-five eyes of 25 patients with NO and age-gender-matched control subjects were enrolled. The mean TCA, SA and LA were found to be significantly higher in patients with NO (2.51 ± 0.44 vs. 1.91 ± 0.35 mm2, P < 0.001; 0.86 ± 0.17 vs. 0.63 ± 0.13 mm2, P < 0.001; and 1.65 ± 0.29 vs. 1.27 ± 0.23 mm2, P < 0.000, respectively). On the contrary, CVI did not significantly differ between the two groups (65.72, 67.68, P = 0.099). CONCLUSION: As a novel OCT-based marker, CVI could be used to assess vascular status of the choroid in eyes with NO and can provide better understanding of the pathogenesis of this disease.

Serum calcium, magnesium, phosphorus, and vitamin D in benign essential blepharospasm.

PURPOSE: This study aims to compare serum calcium, magnesium, phosphorus, and 25-hydroxy (OH)-vitamin D levels in patients with benign essential blepharospasm (BEB) and healthy subjects and to determine their association with disease severity and frequency. METHODS: This is a prospective study conducted in a tertiary care hospital. Fifty patients (female, 39; male, 11) with BEB and 22 healthy subjects (female, 15; male, 7) included in the study. Serum calcium, magnesium, phosphorus, and vitamin D levels of BEB and healthy groups were measured. Blepharospasm severity and frequency were assessed using scales ranging from 0 to 4 by following the Jankovic Rating Scale (JRS). RESULTS: Though there was no significant difference regarding magnesium, phosphorus, and 25(OH)-vitamin D levels between the two groups, serum calcium levels of the BEB group were significantly lower than the control group (9.5 ± 0.4 and 9.9 ± 0.4 mg/dl, respectively; P = 0.002), although in the normal range (9-10.5 mg/dl). In the BEB group, the mean Jankovic severity and frequency scores were 3.29 ± 0.54 and 3.59 ± 0.61, respectively. There was a moderate negative correlation between serum 25(OH)-vitamin D levels and Jankovic severity score (r = - 0.332; P = 0.022). CONCLUSION: Serum calcium levels of the BEB group were significantly lower than the healthy group. Serum vitamin D levels showed a moderate negative correlation with disease severity. The role of calcium and vitamin D in the evolution of the BEB need further investigation at the cellular and anatomical levels.

Retinal microvasculature in the remission period of Behcet's uveitis.

PURPOSE: To evaluate retinal microvasculature and blood flow during Behcet's uveitis (BU) remission via optical coherence tomography angiography (OCT-A), and compare the results with those from healthy eyes. METHODS: A total of 35 eyes of 35 BU patients presenting during the remission period of BU involving the posterior segment were enrolled, as were 30 normal eyes of 30 age and sex-matched healthy participants. Optical coherence tomography angiograms were analyzed. Foveal avascular zone (FAZ), vessel densities, and flow areas were calculated and compared. RESULTS: Thirty-five eyes of 35 BU patients and 30 normal eyes of 30 age and sex-matched subjects were included in the study. The superficial FAZ was slightly higher in the BU group than in the control group (p = 0.01), but deep FAZ was substantially higher (p < 0.001). Deep foveal and parafoveal vessel densities were significantly lower in BU eyes (p < 0.05). Flow areas in superficial and deep plexuses were lower in BU eyes (p < 0.05), however choroidal flow was similar (p > 0.05). CONCLUSION: BU can cause permanent damage especially in the deep capillary plexus and OCT-A provides a detailed view of the retinal microvasculature which helps us to visualize vascular damage in these patients. Further studies with longer follow-up periods are needed to define the role of OCT-A in the decision of treatment efficacy with different agents.

Early and Late Switch from Ranibizumab to an Intravitreal Dexamethasone Implant in Patients with Diabetic Macular Edema in the Event of a Poor Anatomical Response.

BACKGROUND AND OBJECTIVE: Patients with diabetic macular edema may not have optimal outcomes even with monthly ranibizumab intravitreal injections. A corticosteroid implant might be considered in such patients. The objective of this study was to compare the outcomes of switching from ranibizumab to an intravitreal dexamethasone implant after three or six consecutive monthly injections of ranibizumab. METHODS: Patients with treatment-naïve diabetic macular edema who showed a poor anatomical response to three or six consecutive intravitreal ranibizumab injections and received an intravitreal dexamethasone implant were enrolled in this retrospective study. Patients were divided into two groups as early- and late-switch groups. The early-switch group consisted of the patients who initially received three consecutive monthly ranibizumab injections and the late-switch group consisted of the patients who initially received six consecutive monthly ranibizumab injections and switched to a dexamethasone implant because of a poor anatomical response. Best corrected visual acuity and central retinal thickness at the baseline and 3, 6, 9, and 12 months in the study population were recorded. RESULTS: Sixty-eight eyes of 68 patients were included. The early-switch group consisted of 34 eyes and the late-switch group consisted of 34 eyes. The mean change in best corrected visual acuity was similar between the two groups at 3, 9, and 12 months; however, it was significantly better in the early-switch group than the late-switch group at 6 months. The change in central retinal thickness was similar between the two groups at 3, 9, and 12 months; however, it was significantly better in the early-switch group than the late-switch group at 6 months. CONCLUSIONS: Although both early switching and late switching are similar in terms of providing functional and morphological improvement, early switching appeared better for ensuring patient well-being in the early period and improving patient adherence.