Rohit Shetty

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.

Elevated expression of matrix metalloproteinase-9 and inflammatory cytokines in keratoconus patients is inhibited by cyclosporine A.

PURPOSE The present study was designed to understand the role of inflammatory cytokines secreted by corneal epithelial cells in keratoconus (KC) and the response to treatment with cyclosporine A (CyA). METHODS The study involved 129 Indian KC patients clinically graded according to Amsler-Krumeich classification and 20 healthy, nonectatic subjects as controls. Tear levels of matrix metalloproteinase-9 (MMP9), interleukin-6 (IL6), and tumor necrosis factor-α (TNFα) were measured using ELISA kits. Gene expression was measured by qPCR in corneal epithelial cells obtained by debridement from subjects undergoing ocular surface surgeries. In addition, epithelial cells were stimulated with TNFα and treated with CyA to study its role on MMP9 expression. Finally, 20 KC patients (27 eyes) with inflammatory symptoms were treated with topical CyA application. RESULTS We observed that MMP9, TNFα, and IL6 levels were strongly upregulated at the mRNA level in KC patient epithelia. Similarly, tears collected from KC patients exhibited high levels of MMP9 and IL6 protein. Cyclosporine A treatment significantly reduced the mRNA expression levels of IL6 and TNFα in both short- and long-term treatments; however, it reduced MMP9 levels only in long-term treatment in cultured corneal epithelial cells. Subsequent treatment of KC patients with CyA for approximately 6 months reduced tear MMP9 levels and led to local reduction in corneal curvatures as determined by corneal topography maps. CONCLUSIONS The data indicate that corneal epithelium contributes to elevated MMP9 and inflammatory cytokine expression in tears of KC patients. Cyclosporine A treatment reduced MMP9 and inflammatory cytokine levels in an in vitro inflammation model system. In KC patients, CyA treatment reduced MMP9 levels measured in tears with concomitant arrest of disease progression. Therefore, CyA might be a novel treatment strategy in KC patients but requires additional evaluation in larger cohorts. (ClinicalTrials.gov number, NCT01746823.).

Air-puff associated quantification of non-linear biomechanical properties of the human cornea in vivo

With the advent of newer techniques to correct refraction such as flapless laser procedure and collagen crosslinking, in vivo estimation of corneal biomechanical properties has gained importance. In this study, a new 3-D patient specific inverse finite element method of estimating corneal biomechanical properties from air-puff applanation was developed. The highlight of the model was inclusion of patient-specific corneal tomography, fiber dependent hyperelastic model, cross links between collagen lamellae and epithelium layer. A lumped mass, spring and dashpot model was included to model the resistance to motion and deformation of the eye globe caused by air-puff applanation. 10 normal eyes of 10 human subjects were used for the study. 3-D finite element models were constructed and custom routines were scripted for performing the inverse calculations. The model for each eye was perturbed to estimate the effect of measured intraocular pressure on the estimated biomechanical variables. The study demonstrated that the inverse method was effective in quantification of material properties and was sensitive to intraocular pressure alterations. Specifically, in vivo fiber dependent hyperelastic biomechanical properties of human corneas were estimated for the first time.

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.

Recessive Mutations in SLC38A8 Cause Foveal Hypoplasia and Optic Nerve Misrouting without Albinism

Foveal hypoplasia and optic nerve misrouting are developmental defects of the visual pathway and only co-occur in connection with albinism; to date, they have only been associated with defects in the melanin-biosynthesis pathway. Here, we report that these defects can occur independently of albinism in people with recessive mutations in the putative glutamine transporter gene SLC38A8. Nine different mutations were identified in seven Asian and European families. Using morpholino-mediated ablation of Slc38a8 in medaka fish, we confirmed that pigmentation is unaffected by loss of SLC38A8. Furthermore, by undertaking an association study with SNPs at the SLC38A8 locus, we showed that common variants within this gene modestly affect foveal thickness in the general population. This study reveals a melanin-independent component underpinning the development of the visual pathway that requires a functional role for SLC38A8.

Biomechanics of the Cornea Evaluated by Spectral Analysis of Waveforms from Ocular Response Analyzer and Corvis-ST

Purpose In this study, spectral analysis of the deformation signal from Corvis-ST (CoST) and reflected light intensity from ocular response analyzer (ORA) was performed to evaluate biomechanical concordance with each other. Methods The study was non-interventional, observational, cross-sectional and involved 188 eyes from 94 normal subjects. Three measurements were made on each eye with ORA and CoST each and then averaged for each device. The deformation signal from CoST and reflected light intensity (applanation) signal from ORA was compiled for all the eyes. The ORA signal was inverted about a line joining the two applanation peaks. All the signals were analyzed with Fourier series. The area under the signal curves (AUC), root mean square (RMS) of all the harmonics, lower order (LO included 1st and 2nd order harmonic), higher order (HO up to 6th harmonic), CoST deformation amplitude (DA), corneal hysteresis (CH) and corneal resistance factor (CRF) were analyzed. Results The device variables and those calculated by Fourier transform were statistically significantly different between CoST and ORA. These variables also differed between the eyes of the same subject. There was also statistically significant influence of eyes (left vs. right) on the differences in a sub-set of RMS variables only. CH and CRF differed statistically significantly between the eyes of subject (p<0.001) but not DA (p = 0.65). Conclusions CoST was statistically significantly different from ORA. CoST may be useful in delineating true biomechanical differences between the eyes of a subject as it reports deformation.

Visual quality after posterior chamber phakic intraocular lens implantation in keratoconus.

PURPOSE: To quantify image‐quality characteristics after correction of refractive error with a posterior chamber phakic intraocular lens (PC pIOL) in eyes with stable or stabilized keratoconus. SETTING: Narayana Nethralaya Postgraduate Institute of Ophthalmology, Bangalore, India. DESIGN: Case series. METHODS: Eyes with stable or stabilized keratoconus that had V4 Visian PC pIOL implantation for correction of refractive error were evaluated postoperatively for visual‐quality metrics. RESULTS: Ten eyes of 7 patients had PC pIOL implantation. The preoperative mean refractive spherical equivalent of −7.21 diopters (D) ± 2.25 (SD) decreased to −0.55 ± 1.53 D at 6 weeks and −0.44 ± 1.21 D at 6 months. The efficacy index was 0.72 and the safety index, 1.13. The mean modulation transfer function (MTF) was 18.96 ± 14.16 (≥30 cycles per degree = good), the Strehl ratio was 0.11 ± 0.07 (1 = perfect), and the objective scatter index (OSI) was 4.45 ± 3.29 (≥1.5 = significant scatter). The MTF correlated inversely with secondary coma (P=.026), negative vertical coma (P=.014), and the root mean square (RMS) of total aberrations (P=.010) and higher‐order aberrations (HOAs) (P=.015). The OSI was directly correlated with secondary coma (P=.021), secondary trefoil (P=.016), the RMS of total aberrations (P=.032), and HOAs (P=.050). CONCLUSION: In keratoconus, the refractive error could be corrected with the PC pIOL; however, the associated aberrations had an adverse impact on the ultimate visual quality and have to be addressed. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.