Chaitra Jayadev

Current Protocols of Corneal Collagen Cross-Linking: Visual, Refractive, and Tomographic Outcomes

PURPOSE To study the effect of different protocols of collagen cross-linking on visual, refractive, and tomographic parameters in patients with progressive keratoconus. DESIGN Prospective randomized interventional study. METHODS In this study, 138 eyes of 138 patients with progressive keratoconus underwent corneal collagen cross-linking (CXL). Following detailed preoperative examination, Group I underwent conventional cross-linking (36 patients, 3 mW/cm(2) for 30 min); Group II (36 patients, 9 mW/cm(2) for 10 min), Group III (33 patients, 18 mW/cm(2) for 5 min), and Group IV (33 patients, 30 mW/cm(2) for 3 min) underwent accelerated cross-linking. Changes in corrected distance visual acuity (CDVA), spherical equivalent (SE), flat keratometry, steep keratometry, thinnest pachymetry, specular microscopy, and demarcation line were studied at 6 and 12 months. RESULTS Improvement in the mean CDVA and SE were statistically significant in all groups except Group IV (P = .15 at 6 months, P = .17 at 12 months), with Group III (P = .01 at 6 and 12 months) showing the best results. Flattening of steep and flat keratometry was significant in Groups I (P = .01) and II (P = .01) as compared to the other groups. There was no significant difference in the pachymetry or specular microscopy in any of the groups. Groups I and II demonstrated a good demarcation line when compared to other groups. CONCLUSION Conventional CXL (Group I) and accelerated CXL with irradiations of 9 mW/cm(2) (Group II) and 18 mW/cm(2) (Group III) showed better visual, refractive, and tomographic improvements at the end of 12 months.

Collagen crosslinking in the management of advanced non-resolving microbial keratitis

Aim To evaluate the efficacy and safety of corneal collagen crosslinking (CXL) in the management of culture proven microbial keratitis. Methods 15 eyes of 15 patients of microbial keratitis were included in the study. Nine patients had bacterial keratitis and six had fungal keratitis. All patients underwent microbiological evaluation to identify the causative organism. The depth of the infiltrate was determined clinically with slit lamp and measured manually using anterior segment optical coherence tomography. Patients were treated with antibiotics/antifungals and those who did not respond to at least 2 weeks of topical medications underwent CXL as per the standard protocol. The same preoperative topical medications were continued post-CXL. All patients were followed up every third day and observed for signs of resolution of microbial keratitis. Results Six of nine patients with bacterial keratitis and three of six patients with fungal keratitis resolved following CXL treatment. Patients with deep stromal keratitis or endothelial plaque failed to resolve. All patients had resolution of pain on the first postoperative day. There was an appearance of or increase in hypopyon in seven patients. No intraoperative or postoperative complications were noticed. Conclusions CXL appears to be an effective procedure in the management of superficial microbial keratitis. It can be used as an adjunctive treatment in the management of non-resolving microbial keratitis.

Accelerated Corneal Collagen Cross-Linking in Pediatric Patients: Two-Year Follow-Up Results

Purpose. To evaluate the effectiveness and safety of accelerated corneal collagen cross-linking (ACXL) in patients below 14 years of age with progressive keratoconus. Materials and Methods. Thirty eyes of 18 patients with established progressive keratoconus underwent preoperative and postoperative visual acuity assessment, topography, and specular microscopy prior to ACXL and were followed up for 24 months. Results. Mean age of the patients was 12.7 years with ten males and eight females. There was an improvement in the mean postoperative uncorrected distant visual acuity (from 0.76 ± 0.26 to 0.61 ± 0.25; P = 0.005), mean corrected distant visual acuity (from 0.24 ± 0.19 to 0.12 ± 0.12; P < 0.001), mean spherical refraction (from −3.04 DS ± 3.60 to −2.38 DS ± 3.37; P = 0.28), mean cylinder (from −3.63 DC ± 1.82 to −2.80 DC ± 1.48; P = 0.008), and spherical equivalent (from −4.70 D ± 3.86 to −3.75 D ± 3.49; P = 0.15). Three eyes of two patients with vernal keratoconjunctivitis (VKC) showed progression. There were no intra- or postoperative complications. Conclusion. In pediatric patients ACXL is an effective and safe procedure for the management of keratoconus. Optimal management of VKC is important to arrest the progression of keratoconus.

Repeatability and Agreement of Three Scheimpflug-Based Imaging Systems for Measuring Anterior Segment Parameters in Keratoconus

PURPOSE To assess the repeatability and agreement of three rotating Scheimpflug cameras, Pentacam, Galilei, and Sirius, in measuring the mean keratometry (Km), thinnest corneal thickness (TCT), anterior chamber depth (ACD), and mean posterior keratometry (pKm) in keratoconus patients in a prospective study. METHODS Fifty-five eyes of 55 patients with keratoconus underwent three consecutive scans on each machine, performed by a single operator. Within-subject standard deviation (Sw), test-retest repeatability (TRT), and coefficient of variation (COV) for assessing repeatability and Bland-Altman plots for the agreement between the mean measurements of each machine were examined. RESULTS The Sw of Km and pKm measurements with Pentacam (0.23 and 0.10 diopters [D], respectively) were significantly lower (better) than those of Galilei (0.60 and 0.17) and Sirius (0.23 and 0.36). The Sw of TCT measurements with Sirius (8.88 μm) was significantly lower than that of Galilei (11.64 μm). The COV ranged between 0.5 for the Km measurements of Pentacam and 2.8 for the TCT measurements of Galilei. Significant proportional bias in agreement was detected for the pKm measurements with all the three device pairs and for the ACD measurements between Pentacam and Galilei and between Galilei and Sirius. CONCLUSIONS Though Pentacam, Galilei, and Sirius showed repeatable measurements for Km, TCT, ACD, and pKm, repeatabilities with Pentacam and Sirius were better than those with Galilei. There were significant differences in the measurements between the three devices; hence they cannot be used interchangeably for anterior segment measurements in keratoconus patients.

Characteristics and quantification of vascular changes in macular telangiectasia type 2 on optical coherence tomography angiography

Background Macular telangiectasia type 2 (MacTel 2) is a bilateral idiopathic, rare neurodegenerative disease with alterations in the macular capillary network leading to vision loss and is the most common of three subtypes. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality which helps understand the complex pathological changes, and images the blood vessels across different layers based on their flow characteristics. Methods A cross-sectional study was conducted on 56 eyes of Asian Indian eyes of 28 consecutive patients with MacTel 2 studied during a 3-month period in a tertiary eye care hospital of South India. Clinically diagnosed cases of MacTel 2 underwent fundus photography, spectral domain OCT and OCTA. Fluorescein angiography was performed only when clinically indicated. Mean capillary density was calculated using a MATLAB-based automated software. The images were thresholded and binarised to derive the mean value. Results The mean age at presentation was 60±5.2, with a female preponderance of 71.42%. Vascular network on OCTA shows an increase in the intervascular spaces with progressive capillary rarefaction and abnormal capillary anastomosis. The outer retina and choroid were involved during the later stages and showed a prominent vascular network. The mean capillary density of the superficial and deep layers was 39.99% and 39.03% as against 45.18% and 44.21% in the controls, respectively. There was a statistically significant difference between the two groups (p<0.01). There is a positive and statistically significant correlation between the superficial and deep layers. Conclusion OCTA helps understand the pathology and disease progression better in MacTel 2.

Nanostructured scaffold as a determinant of stem cell fate

The functionality of stem cells is tightly regulated by cues from the niche, comprising both intrinsic and extrinsic cell signals. Besides chemical and growth factors, biophysical signals are important components of extrinsic signals that dictate the stem cell properties. The materials used in the fabrication of scaffolds provide the chemical cues whereas the shape of the scaffolds provides the biophysical cues. The effect of the chemical composition of the scaffolds on stem cell fate is well researched. Biophysical signals such as nanotopography, mechanical forces, stiffness of the matrix, and roughness of the biomaterial influence the fate of stem cells. However, not much is known about their role in signaling crosstalk, stem cell maintenance, and directed differentiation. Among the various techniques for scaffold design, nanotechnology has special significance. The role of nanoscale topography in scaffold design for the regulation of stem cell behavior has gained importance in regenerative medicine. Nanotechnology allows manipulation of highly advanced surfaces/scaffolds for optimal regulation of cellular behavior. Techniques such as electrospinning, soft lithography, microfluidics, carbon nanotubes, and nanostructured hydrogel are described in this review, along with their potential usage in regenerative medicine. We have also provided a brief insight into the potential signaling crosstalk that is triggered by nanomaterials that dictate a specific outcome of stem cells. This concise review compiles recent developments in nanoscale architecture and its importance in directing stem cell differentiation for prospective therapeutic applications.

Safety profile of accelerated corneal cross-linking versus conventional cross-linking: a comparative study on ex vivo-cultured limbal epithelial cells

Aim/background To compare the effects of accelerated corneal collagen cross-linking (ACXL) and corneal collagen cross-linking (CXL) on ex vivo-cultured limbal epithelial cells (LECs). Methods Day 14 cultured LECs were either unexposed (control) or exposed to different intensities of ultraviolet-A (UV-A) irradiance for different durations (3 mW for 30 min, 9 mW for 10 min, 18 mW for 5 min and 30 mW for 3 min) in the presence and absence of riboflavin. These cells were further processed for quantitative real-time PCR, vital staining, immunofluorescence staining and fluorescence-activated cell sorting (FACS) staining to evaluate the apoptotic status. Statistical analysis was performed using a Student t test. Results Vital staining showed a significantly higher (p=0.004) dead cell population with 3 mW for 30 min when compared with 30 mW for 3 min exposure (p=0.225). Quantitative PCR results revealed significantly reduced abcg2 and Δnp63 mRNA levels, while FACS analysis showed an increase in ABCG2-Annexin V positive population in cells exposed to 3 mW for 30 mins. Neither reduction of mRNA expression of abcg2 and Δnp63 nor increase in FACS-stained ABCG2-Annexin V positivity was detected in cells exposed to 30 mW for 3 min. Additionally, enhanced caspase activity was detected with fluorochrome inhibitor of caspases staining and mRNA expression of caspase 3 and 9 was upregulated in cells exposed to 3 mW for 30 min, but not at 30 mW for 3 min. Conclusions The 30 mW UV-A irradiation used in ACXL appears to be safe on cultured LECs in comparison with 3 mW used in CXL.

Corneal Densitometry: Repeatability in Eyes With Keratoconus and Postcollagen Cross-Linking.

Purpose: To assess the repeatability of densitometry, a measure of corneal haze, in the control (group I), keratoconic (group II), and postcollagen cross-linking (CXL, group III) eyes as measured on Scheimpflug imaging. Methods: Densitometry values for 160 eyes of 160 patients (50 eyes of 50 patients in group I, 50 eyes of 50 patients in group II, and 60 eyes of 60 patients in group III) were obtained for the 0- to 2-mm, 2- to 6-mm, and 6- to 10-mm zones of the anterior (up to 120 &mgr;m), posterior (posterior 60 &mgr;m), and central (between the anterior and posterior) cornea. The repeatability of these values was assessed by within-subject standard deviation, coefficient of repeatability, and coefficient of variation. Results: Range of within-subject standard deviation and coefficient of variation in the control group (0.2%–0.5% and 2%–4%, respectively) was significantly better (less variable) than those in the keratoconus group (0.4%–0.6% and 3%–5%). The same parameters in the post-CXL group (0.8%–3.8% and 7%–15%) were significantly worse (more variable) than that in the other 2 groups. The repeatability measures of densitometry were significantly worse in the central 0- to 2-mm zone compared with the other 2 zones and for the anterior region compared with the central and posterior regions of cornea in all the 3 groups. Conclusions: Consequent to the low repeatability in post-CXL eyes, densitometry should be used with caution to gauge response to treatment and visual outcomes in treated keratoconus eyes.

The use of handheld spectral domain optical coherence tomography in pediatric ophthalmology practice: Our experience of 975 infants and children.

Purpose: Optical coherence tomography (OCT) is an important imaging tool assessing retinal architecture. In this article, we report a single centers experience of using handheld spectral domain (SD)-OCT in a pediatric population using the Envisu 2300 (Bioptigen Inc., Research Triangle Park, NC, USA). Methods: We studied SD-OCT images from 975 patients imaged from January 2011 to December 2014. The variety of cases that underwent an SD-OCT was analyzed. Cases examples from different case scenarios were selected to showcase unique examples of many diseases. Results: Three hundred and sixty-eight infants (37.7%) were imaged for retinopathy of prematurity, 362 children (37.1%) underwent the test for evaluation of suboptimal vision or an unexplained vision loss, 126 children (12.9%) for evaluation of nystagmus or night blindness, 54 children (5.5%) for an intraocular tumor or a mass lesion such as retinoblastoma, and 65 children (6.7%) for other diseases of the pediatric retina. The unique findings in the retinal morphology seen with some of these diseases are discussed. Conclusion: The handheld SD-OCT is useful in the evaluation of the pediatric retinal diseases. The test is useful in the assessment of vision development in premature children, evaluation of unexplained vision loss and amblyopia, nystagmus and night blindness, and intraocular tumors (including retinoblastoma).

Current review and a simplified "five-point management algorithm" for keratoconus

Keratoconus is a slowly progressive, noninflammatory ectatic corneal disease characterized by changes in corneal collagen structure and organization. Though the etiology remains unknown, novel techniques are continuously emerging for the diagnosis and management of the disease. Demographical parameters are known to affect the rate of progression of the disease. Common methods of vision correction for keratoconus range from spectacles and rigid gas-permeable contact lenses to other specialized lenses such as piggyback, Rose-K or Boston scleral lenses. Corneal collagen cross-linking is effective in stabilizing the progression of the disease. Intra-corneal ring segments can improve vision by flattening the cornea in patients with mild to moderate keratoconus. Topography-guided custom ablation treatment betters the quality of vision by correcting the refractive error and improving the contact lens fit. In advanced keratoconus with corneal scarring, lamellar or full thickness penetrating keratoplasty will be the treatment of choice. With such a wide spectrum of alternatives available, it is necessary to choose the best possible treatment option for each patient. Based on a brief review of the literature and our own studies we have designed a five-point management algorithm for the treatment of keratoconus.