[The effect of keratoconus-associated refractive errors on the results of tomographic methods of studying the posterior structures of the eye]. / Vliyanie opticheskikh narushenii pri keratokonuse na rezul'taty tomograficheskikh metodov issledovaniya struktur zadnego segmenta glaza.

PURPOSE: The study assesses the potential influence of refractive errors in keratoconus (KC) on the results of tomographic methods of studying the structures of the posterior eye segment. MATERIAL AND METHODS: The study included 30 patients with bilateral stabilized KC of stages I-IV in classification by M. Amsler. Spherical and cylindrical components of refractions were determined using automatic refractometry, keratometry measurements - based on scanning keratotopography with Scheimpflug analyzer. Aberrometry was performed to evaluate corneal wave front according to the following parameters: root mean square for lower order aberrations (RMS LOA), root mean square for higher order aberrations (RMS HOA), vertical trefoil, vertical coma, horizontal coma and spherical aberrations. Optical coherence tomography (OCT) and laser confocal scanning ophthalmoscopy (HRT 3) data was used in morphometric analysis of the optic nerve head and peripapillary retina. The following morphometric parameters were analyzed: optic nerve head (ONH) area, optic disc cup area, optic disc cup volume, ratio of optic disc cup area to ONH area, neuroretinal rim area, neuroretinal rim volume, peripapillary retinal nerve fiber layer (RNFL) thickness. All studies were performed first without correction, and 30 minutes after installing customized scleral hard contact lenses (SHCL). RESULTS: Compensation of the refractive errors characteristic for KC was achieved as expected with contact correction. OCT revealed a general trend for reduction in the area and volume of the optic disc cupping, ratio of area to volume of the optic disc cupping, as well as an increase in other parameters. As such, with correction the values for area and volume of the neuroretinal rim according to OCT were 2.2 and 13%, HRT 3 - 18 and 51.6%; comparable increase in mean RNFL thickness - 2.8 and 28.5%, respectively (p<0.001). According to HRT 3 data, the area and volume of optic disc cupping statistically significantly decreased (by 21 and 28%, respectively), while OCT showed statistically significant decrease only in cupping area (by 5.7%). The ratio of cupping to ONH area decreased by 6.6 and 23% relative to the initial data obtained with OCT and HRT 3, respectively. Significant decrease in ONH area amid SHCL correction was observed only with HRT 3. The revealed changes in morphometric parameters were analyzed using the fundamental principles of physiological optics. Changes in interference pattern and, consequently, morphometric parameters of structures of the eye fundus in KC are of multifactorial nature, and are mostly associated with refractive and wave artefacts occurring when the rays pass through the irregular corneal surface and cannot be optically compensated by the device. The use of SHCL as means for making the optic system relatively regular can significantly decrease the artefacts in morphometric measurements. CONCLUSION: The results obtained in this study demonstrate the practicality of tomographic examination in KC with contact correction. The optimal choice is custom-fit SHCL, which along with proper correction of refractive errors also ensures stable position of the lens on the cornea. In standard examination specialists should take into account the «false¼ decrease in parameters of the peripapillary retinal nerve fiber layer and increase in ONH cupping.

Transepithelial corneal crosslinking with oxygen enhancement and pulsed light for progressive ectasia: one-year results.

PURPOSE: To evaluate the efficacy and safety of transepithelial accelerated crosslinking (TE-ACXL) using pulsed light and supplemental oxygen. METHODS: Thirty eyes of 30 consecutive patients with progressive keratoconus or post-LASIK ectasia were enrolled in a prospective non-comparative study conducted at the Magrabi Eye Center (Jeddah, Saudi Arabia). All eyes underwent TE-ACXL with supplemental oxygen. Primary outcome measures were the mean change in corrected distance visual acuity (CDVA) (logMAR) and maximum keratometry (max K) from preoperatively to 12 months postoperatively. Secondary outcome measures included change in manifest refractive spherical equivalent (MRSE), refractive cylinder, keratometry, symmetry index (SI), center-surrounding index (CSI) and ectasia index (EI) of the anterior and posterior corneal surfaces, corneal and epithelial thickness at corneal vertex and thinnest location, corneal densitometry, corneal high order aberrations (HOA) and endothelial cell density (ECD). RESULTS: Mean age was 29.6 ± 8.2 years. At 1 year, the follow up rate was 93.3%. CDVA improved statistically significantly at 12 months (p = 0.027). Measures of corneal keratometry or pachymetry did not change significantly (p < 0.05). Postoperatively, a demarcation line was documented in 78.6% eyes at 1 month, and in 12 (42.9%) eyes at 12 months. The mean depth of the demarcation line was 341.9 ± 49.4 µm. Corneal densitometry increased significantly at 1- and 3-months (p < 0.05) and returned to normal levels at 6- and 12-months postoperatively. CONCLUSION: TE-ACXL with oxygen supplement is effective at halting the progression of corneal ectasia for at least 1 year and can be a refractive neutral procedure.

Association of keratoconus with serum levels of 25-hydroxyvitamin D and antioxidant trace elements: A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to summarize and compare the available evidence on the level of vitamin D and antioxidant trace elements between the keratoconus (KC) patients and healthy controls. Seven case-control studies with 830 subjects were found eligible with a systematic search using PubMed, SCOPUS, Web of Science, and EMBASE till November 21, 2021. Data were synthesized with a DerSimonian and Laird random-effects method of meta-analysis. The mean serum vitamin D level was significantly lower in the patients with KC [standardized mean difference (SMD): -0.71; P < 0.001] as compared with the control group. The mean serum vitamin D level decreased more in the progressive patients (SMD: -0.80; P = 0.016) than in the stable patients (SMD: -0.66; P < 0.001) when compared with the control group. The mean serum zinc level was found significantly lower in the patients with KC compared with the control group (SMD: -1.98; P = 0.005). Pooled analysis based on the two studies showed significantly lower mean selenium levels in the KC patients (SMD: -0.34; P = 0.003). Regular evaluation of serum vitamin D, zinc, and selenium levels among the patients with KC at disease onset and future follow-ups could be promising in predicting the progressive disease and disease severity.

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.

Comparison of Continuous versus Pulsed Mode in Accelerated Corneal Collagen Cross-linking for Keratoconus.

PURPOSE: To compare efficacy and safety between the two modes of energy delivery-pulsed and continuous, in accelerated corneal collagen cross-linking (KXL) to stop the keratoconus advancement through topographical, visual, and refractive endpoints. METHODS: It was a prospective, comparative, randomized, interventional trial. Patients with bilateral progressive keratoconus were subjected to pulsed mode KXL (P-KXL) in the right and continuous mode KXL (C-KXL) treatment in the left eye. In both methods, additional supplemental oxygen was delivered to corneal surface using a nasal cannula connected to an oxygen supply. Uncorrected distance visual acuity (UDVA) and corrected distance visual acuity, posttreatment manifest spherical equivalent and astigmatism, and corneal topography were studied. The deformation amplitude index (DAI) was measured by Corvis-ST. Postoperative follow-up was done. RESULTS: One hundred eyes of 50 patients underwent P-KXL in the right eye and C-KXL in the left eye. The average follow-up was 12.1 ± 1.2 months. At 1 year posttreatment, the UDVA had a mean change of 0.11 ± 0.14 logMAR in P-KXL and 0.18 ± 0.14 logMAR in C-KXL groups. The line of demarcation was observed at 251.13 ± 18.28 µ and 245.28 ± 28.26 µ deep, respectively, in P-KXL- and C-KXL-treated eyes at 6 months' follow-up. The DAI as measured by Corvis-ST showed a significant decrease from pretreatment values of 1.12 ± 0.13 mm to 0.84 ± 0.14 mm (P < 0.01) in P-KXL eyes and from 1.04 ± 0.14 mm to 0.85 ± 0.15 mm (P = 0.03) in C-KXL eyes. Both the groups did not show any statistically significant endothelial cell loss posttreatment. CONCLUSION: C-KXL can give similar functional outcomes as P-KXL with the help of supplemental oxygen delivery with the added advantage of a shortened procedure time in comparison to pulsed mode.

Eye Rubbing and Transient Corneal Ectasia Detected by Topography in a Pediatric Patient.

ABSTRACT: We report on a 13-year-old girl undergoing changes in the refraction of her OS associated with eye rubbing. Corneal topography showed a corneal deformation in OS, classified as stage 1 keratoconus according to the Krumeich classification. A significant reduction in eye rubbing led to a normal corneal shape at the 1-year follow-up. Transient and fully reversible corneal ectasia can be caused by eye rubbing in pediatric age. This may have implications when counseling very young patients with eye rubbing.

Association of retinitis pigmentosa and advanced keratoconus in siblings.

Objective. The aim of the article was to present the rare association of retinitis pigmentosa and bilateral keratoconus in two brothers, one of whom developed corneal hydrops bilaterally, within a short period of time. Methods. A 29-year-old man presented to our service with corneal hydrops in the right eye, complaining of ocular pain and photophobia. He had a history of retinitis pigmentosa, having been diagnosed as an infant. He also had a younger brother carrying the same diagnosis. Slit lamp examination revealed bilateral keratoconus with corneal hydrops in the right eye, posterior subcapsular cataract, macular atrophy and the characteristic retinal signs of retinitis pigmentosa. The patient's brother was also examined, with the same findings being noted, apart from the corneal hydrops. We documented the changes using a slit lamp biomicroscope, a fundus camera, a corneal topography, Anterior Segment Optical Coherence Tomography and visual field testing. Right hydrops regressed in one month after hyperosmolar 5% sodium chloride treatment. However, 4 weeks later, the patient presented with the same corneal findings in the left eye. The same treatment was prescribed for the left eye. Results. Corneal hydrops regressed in both eyes with remaining paracentral corneal scars. However, no other treatment for keratoconus was suitable in the case of this patient. Discussion: Retinitis pigmentosa is currently not amenable to any form of treatment, from vitamin supplementation, medical therapy, gene transfer-based therapy, stem cell-based therapy to retinal implantation. However, molecular genetics may someday provide new therapeutic prospects, that could modify the course of RP. Conclusions. The association of retinitis pigmentosa with keratoconus is a fairly rare finding, worth taking into consideration. Also, presentation with keratoconus in such an advanced state is uncommon and, in our case, it was presumably due to the patient's reduced visual function since childhood, secondary to retinitis pigmentosa, that has prevented him from perceiving any visual modifications caused by keratoconus.

Optimization of Oxygen Dynamics, UV-A Delivery, and Drug Formulation for Accelerated Epi-On Corneal Crosslinking.

Purpose: Corneal collagen crosslinking (CXL) through an intact epithelium (epi-on) at high irradiance could potentially improve patient comfort, visual recovery, and clinical workflow compared to conventional epi-off CXL. However, intact epithelium limits stromal delivery of the oxygen, photosensitizer, and ultraviolet-A (UV-A) radiation needed to drive CXL. This ex vivo study evaluated three different epi-on CXL protocols compared to positive and negative controls, specifically focusing on the impact of supplemental oxygen. Endpoints included stromal oxygen levels, stiffness of crosslinked tissue, and acute flattening of whole eyes.Materials & Methods: Ex vivo porcine eyes were held in a custom environmental chamber. Intrastromal oxygen levels were continuously measured before, during, and after UV illumination by a fiberoptic probe inserted into a laser-cut flap. Accelerated, high irradiance, epi-on CXL protocols using riboflavin formulated with benzalkonium chloride (BAC) were studied, with and without supplemental oxygen. These were compared to an alternate, low irradiance, epi-on protocol using riboflavin formulated with sodium iodide. Both negative (no CXL) and positive (epi-off modified Dresden protocol) controls were performed. Post-CXL elastic modulus was measured using extensiometry and anterior tangential curvature was measured using a Scheimpflug tomographer.Results: Protocols including supplemental oxygen resulted in an approximately 5-fold increase in stromal oxygen levels prior to CXL. During epi-on, high-irradiance UV-A delivery under hyperoxic conditions, an aerobic state was maintained. Conversely, under normoxic conditions, stromal oxygen rapidly depleted to 0-5% for all other protocols. The combination of supplemental oxygen, BAC formulation, and high-irradiance UV-A resulted in the largest biomechanical changes and most pronounced flattening effects of the three epi-on protocols.Conclusions: Ex vivo analysis of stromal oxygen levels, corneal stiffness, and acute anterior curvature change indicates that simultaneous optimization of the oxygen environment, riboflavin formulation, and UV-A protocol can significantly increase the effects of corneal collagen crosslinking.

Superior outcome of corneal collagen cross-linking using riboflavin with methylcellulose than riboflavin with dextran as the main supplement.

PURPOSE: To compare the effect of corneal collagen cross-linking (CXL) on progressive keratoconus using 0.1% riboflavin with either dextran or methylcellulose as the main supplement. METHODS: In a comparative case series, CXL was performed in 40 patients (40 eyes) using a riboflavin solution containing either dextran (dextran-riboflavin; n = 20) or methylcellulose (methylcellulose-riboflavin; n = 20). Changes in central corneal thickness (CCT), Scheimpflug tomography, maximal keratometry reading (Kmax ), visual acuity (VA) and endothelial cell density (ECD) were recorded. Stromal changes one month after surgery were analysed using optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM). RESULTS: The CCT was significantly higher in the methylcellulose-riboflavin group during the CXL procedure. The IVCM demarcation line depth was 274 ± 80 (SD) µm in the dextran-riboflavin group and 442 ± 80 µm in the methylcellulose-riboflavin group (p < 0.001). Complete absence of keratocytes in the pre-endothelial stroma was found in none of the corneas treated with dextran-riboflavin and in 42% of the corneas treated with methylcellulose-riboflavin. Visibility of the OCT demarcation line was significantly lower in the methylcellulose-riboflavin group. Kmax and corrected distance visual acuity were improved in the methylcellulose-riboflavin group and stable in the dextran-riboflavin group after 2 years. Endothelial cell density (ECD) was stable in both groups. CONCLUSION: We found deeper structural changes in the methylcellulose-riboflavin group than in the dextran-riboflavin group. This may be explained by different riboflavin solution properties and raises safety concerns. The study also indicates improved effect using methylcellulose-riboflavin than dextran-riboflavin, possibly explained by deeper stromal CXL effect.

The Youngest Patient with Bilateral Keratoconus Secondary to Chronic Persistent Eye Rubbing.

We present the case of a four-year-old girl with bilateral keratoconus secondary to chronic persistent eye rubbing. She was referred to our clinic with intractable ocular itching and low vision. According to her family, she was generally rubbing her eyes. On slit-lamp biomicroscopic examination, bilateral papillary reactions were seen on the upper tarsal conjunctiva. Clinical examination and corneal topography were compatible with keratoconus. The patient's visual acuity was not evaluated because of cooperation difficulties. Systemic examination was normal. In fact, trauma may be the common underlying factor in eye rubbing and may cause development of keratoconus, even in the early years. To the best of our knowledge, this is the youngest patient with bilateral keratoconus secondary to chronic persistent eye rubbing in the literature. Keratoconus should be kept in mind in patients with severe ocular itching, even in small children.

Gross cystic disease fluid protein-15/prolactin-inducible protein as a biomarker for keratoconus disease.

Keratoconus (KC) is a bilateral degenerative disease of the cornea characterized by corneal bulging, stromal thinning, and scarring. The etiology of the disease is unknown. In this study, we identified a new biomarker for KC that is present in vivo and in vitro. In vivo, tear samples were collected from age-matched controls with no eye disease (n = 36) and KC diagnosed subjects (n = 17). Samples were processed for proteomics using LC-MS/MS. In vitro, cells were isolated from controls (Human Corneal Fibroblasts-HCF) and KC subjects (Human Keratoconus Cells-HKC) and stimulated with a Vitamin C (VitC) derivative for 4 weeks, and with one of the three transforming growth factor-beta (TGF-ß) isoforms. Samples were analyzed using real-time PCR and Western Blots. By using proteomics analysis, the Gross cystic disease fluid protein-15 (GCDFP-15) or prolactin-inducible protein (PIP) was found to be the best independent biomarker able to discriminate between KC and controls. The intensity of GCDFP-15/PIP was significantly higher in healthy subjects compared to KC-diagnosed. Similar findings were seen in vitro, using a 3D culture model. All three TGF-ß isoforms significantly down-regulated the expression of GCDFP-15/PIP. Zinc-alpha-2-glycoprotein (AZGP1), a protein that binds to PIP, was identified by proteomics and cell culture to be highly regulated. In this study by different complementary techniques we confirmed the potential role of GCDFP-15/PIP as a novel biomarker for KC disease. It is likely that exploring the GCDFP-15/PIP-AZGP1 interactions will help better understand the mechanism of KC disease.

Keratoconus caused by eye rubbing in patients with Tourette Syndrome.

OBJECTIVE: To report the association between keratoconus and Tourette Syndrome (TS) and to reinforce that eye rubbing may be a causative factor for keratoconus. DESIGN: Observational case series. PARTICIPANTS: Three patients with TS who presented with clinical and topographic findings suggestive of asymmetric or unilateral keratoconus. METHODS: Evaluation of patients in a single clinical practice. RESULTS: Patients' histories revealed asymmetric or unilateral rubbing of the affected eye as a result of a TS tic. Other organic causes associated with keratoconus were absent in these patients. CONCLUSIONS: A possible association between TS and keratoconus exists with chronic eye rubbing being the suggested mechanism. Eye rubbing seems to be an important causative factor for keratoconus.

Asymmetric keratoconus attributed to eye rubbing.

PURPOSE: To report a series of cases with asymmetric keratoconus attributed to eye rubbing, discuss its pathogenesis, and review the literature. METHODS: Case reports and literature review. RESULTS: A careful history obtained from 5 patients with asymmetric keratoconus revealed habitual eye rubbing of the more severely affected eye. CONCLUSIONS: Trauma, such as occurs with habitual eye rubbing, plays a role in the pathogenesis of keratoconus.