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Oxygen Diffusion May Limit the Biomechanical Effectiveness of Iontophoresis-Assisted Transepithelial Corneal Cross-linking
Torres-Netto, Emilio A; Kling, Sabine; Hafezi, Nikki; Vinciguerra, Paolo; Randleman, J Bradley; Hafezi, Farhad
PURPOSE/OBJECTIVE:To evaluate the impact of varying treatment time on the efficacy of iontophoresis-assisted transepithelial corneal cross-linking (I-CXL) in ex vivo porcine corneas. METHODS:, or were not irradiated (controls). Elastic modulus and stress after relaxation of 5-mm wide corneal strips were analyzed. RESULTS:for 60 minutes setting (group 4) showed a significant stiffening effect. All epithelium-off groups provided a stiffening effect significantly stronger than I-CXL: with a stiffening effect of 149% and 112%, groups 1 and 4 were the groups with greater elastic modulus between the S-CXL and I-CXL groups, respectively. CONCLUSIONS:The biomechanical effect of I-CXL increased significantly when using a low irradiance/long irradiation setting. Oxygen diffusion thus represents a limiting factor even when riboflavin penetration is improved via iontophoresis. Still less effective than S-CXL, this modification may help establish transepithelial CXL as a treatment option in selected cases. [J Refract Surg. 2018;34(11):768-774.].
PMID: 30428097
ISSN: 1081-597x
CID: 5484242
Prevalence of keratoconus in paediatric patients in Riyadh, Saudi Arabia
Torres Netto, Emilio Almeida; Al-Otaibi, Wafa Majed; Hafezi, Nikki L; Kling, Sabine; Al-Farhan, Haya M; Randleman, J Bradley; Hafezi, Farhad
BACKGROUND/AIM:Keratoconus (KC) is a ectatic corneal disorder with marked progression during childhood and puberty that may lead to severe visual loss. In addition to KC prevalence, estimate shows major geographical variations; recent studies using Scheimpflug technology are in contrast to the 1980s and 1990s literature. The present study aims to determine the prevalence of KC in paediatric patients in Riyadh, Saudi Arabia (KSA). METHODS:This prospective, cross-sectional, observational, multicentre study collected data from paediatric patients from 6 years and 21 years of age who were seen at multiple non-ophthalmic emergency departments within KSA. Bilateral corneal measurements were performed using a rotational Scheimpflug corneal tomography system. Two masked examiners established the diagnosis of KC using both objective and subjective screening criteria. Cohen's kappa coefficient (κ) was used to qualitatively analyse the interexaminer agreement. RESULTS:There were 522 patients (1044 eyes) evaluated, with an average age of 16.8±4.2 years (range 6-21 years). KC prevalence was 5.56% for examiner 1 and 3.83% for examiner 2. The κ was 0.81 (almost perfect agreement), with discrepancy in nine cases, which were jointly evaluated and consensus obtained. Final KC prevalence was 4.79% (95% CI 2.96 to 6.62) or 1:21 patients. CONCLUSIONS:The prevalence of KC among paediatric patients in the KSA is considerably higher than numbers reported from earlier studies and from similar studies in other countries. This increase might be due to geographical variations in disease prevalence or due to the ability of screening technology to detect undiagnosed KC with greater accuracy.
PMID: 29298777
ISSN: 1468-2079
CID: 5484162
Corneal Cross-Linking: Current USA Status: Report From the Cornea Society
Belin, Michael W; Lim, Li; Rajpal, Rajesh K; Hafezi, Farhad; Gomes, Jose A P; Cochener, Beatrice
The initial published clinical report on riboflavin/ultraviolet A corneal cross-linking (CXL) for treatment of progressive keratoconus dates back to 2003. CXL has since then been widely used outside the United States for treatment of progressive keratoconus and post-laser in situ keratomileusis ectasia. The Food and Drug Administration (FDA) approved Avedro Inc.'s corneal cross-linking system (KXL) for treatment of patients with progressive keratoconus and post-laser in situ keratomileusis ectasia in April 2016. The procedure is not currently approved for stable keratoconus. There are 2 FDA-approved topical ophthalmic solutions for use in CXL. Riboflavin 5'-phosphate in 20% dextran ophthalmic solution 0.146% (Photrexa Viscous) and Riboflavin 5'-phosphate ophthalmic solution 0.146% (Photrexa) are intended for use with the KXL system. Photrexa Viscous is used in all CXL procedures, whereas Photrexa is indicated for use when the corneal stroma is thinner than 400 µm after completion of the Photrexa Viscous induction period. The FDA-approved procedure using the Dresden protocol (UV-A, 3 mW/cm for 30 min) induces cytologic and morphologic changes in the anterior 250 to 300 µm of the corneal stroma. It has been believed that a minimum thickness of 400 μm was necessary to protect the corneal endothelium from potential damage. The CXL procedure using the standard Dresden protocol is established as the gold standard for treatment of progressive keratoconus. CXL treatment is indicated for a list of conditions ranging from corneal ectasia to infectious keratitis. Newer protocols, treatment regimens, and expanded indications will require further refinements, investigations, and long-term studies.
PMID: 30067537
ISSN: 1536-4798
CID: 5484232
Comparing Change in Anterior Curvature After Corneal Cross-linking Using Scanning-slit and Scheimpflug Technology
Lang, Paul Z; Thulasi, Praneetha; Khandelwal, Sumitra S; Hafezi, Farhad; Randleman, J Bradley
PURPOSE:To evaluate the correlation between anterior axial curvature difference maps following corneal cross-linking (CXL) for progressive keratoconus obtained from Scheimpflug-based tomography and Placido-based topography. DESIGN:Between-devices reliability analysis of randomized clinical trial data. METHODS:for 30 minutes). Regularization index (RI), absolute maximum keratometry (K Max), and change in K Max (ΔK Max) were compared between the 2 devices at each time point. RESULTS:Fifty-one eyes from 36 patients were evaluated at all time points. Values were significantly different at all time points (56.01 ± 5.3 diopters [D] Scheimpflug vs 55.04 ± 5.1 D scanning-slit preoperatively [P = .003]; 54.58 ± 5.3 D Scheimpflug vs 53.12 ± 4.9 D scanning-slit at 12 months [P < .0001]) but strongly correlated between devices (r = 0.90-0.93) at all time points. The devices were not significantly different at any time point for either ΔK Max or RI but were poorly correlated at all time points (r = 0.41-0.53 for ΔK Max, r = 0.29-0.48 for RI). At 12 months, 95% limits of agreement were 7.51 D for absolute K Max, 8.61 D for ΔK Max, and 19.86 D for RI. CONCLUSIONS:Measurements using Scheimpflug and scanning-slit Placido-based technology are correlated but not interchangeable. Both devices appear reasonable for separately monitoring the cornea's response to CXL; however, caution should be used when comparing results obtained with one measuring technology to the other.
PMID: 29729256
ISSN: 1879-1891
CID: 5484202
Biomechanical Properties of Human Cornea Tested by Two-Dimensional Extensiometry Ex Vivo in Fellow Eyes: Femtosecond Laser-Assisted LASIK Versus SMILE
Spiru, Bogdan; Kling, Sabine; Hafezi, Farhad; Sekundo, Walter
PURPOSE/OBJECTIVE:To investigate the biomechanical properties of the ex vivo human cornea after flap-based versus cap-based laser refractive surgery in the same donor. METHODS:In this experimental study, 11 pairs of human corneas unsuitable for transplantation were equally divided into two groups. Corneas from the right eye were treated with femtosecond laser-assisted LASIK (FSLASIK) and corneas from the left eye with small incision lenticule extraction (SMILE). Pachymetry was measured in each eye directly before laser refractive surgery. All corneas were subjected to a refractive correction of -10.00 diopters (D) sphere and -0.75 D cylinder at 0° with a 7-mm zone, using either a 110-μm flap (FS-LASIK) or 130-μm cap (SMILE). For two-dimensional biomechanical measurements, corneoscleral buttons underwent two testing cycles (preconditioning stress-strain curve from 0.03 to 9.0 N and stress-relaxation at 9.0 N during 120 sec) to analyze the elastic and viscoelastic material properties. The effective elastic modulus was calculated. Statistical analysis was performed with a confidence interval of 95%. RESULTS:In stress-strain measurements, the effective elastic modulus was 1.47 times higher (P = .003) after SMILE (median = 8.22 [interquartile range = 4.76] MPa) compared to FS-LASIK (median = 5.59 [inter-quartile range = 2.77] MPa). The effect size was large (r = 0.83). No significant differences (P = .658) were observed among stress-relaxation measurements, with a mean remaining stress of 181 ± 31 kPa after SMILE and 177 ± 26 kPa after FS-LASIK after relaxation. CONCLUSIONS:Compared to a flap-based procedure such as FS-LASIK, the SMILE technique can be considered superior in terms of biomechanical stability, when measured experimentally in ex vivo human fellow eye corneas. [J Refract Surg. 2018;34(6):419-423.].
PMID: 29889296
ISSN: 1081-597x
CID: 5484222
Lower Lateral Cartilage Cephalic Malposition: An Over-Diagnosed Entity
Hafezi, Farhad; Naghibzadeh, Bijan; Kazemi Ashtiani, Abbas
BACKGROUND:Lower lateral cartilage malposition is represented by anterior convexity of the lower lateral cartilage (LLC) dome with posterior pinch, as defined by Sheen and Constantian. This anatomic variation consists of cephalic, or upward and inward, rotation of lateral crura, particularly in bulbous tip patients. In most cases, "bulbous pinch" LLC is positioned toward the medial canthus, not laterally, so it is referred to as cephalic displacement. Accordingly, it is recommended to caudally displace cartilage in the majority of rhinoplasty cases in which variation is seen. OBJECTIVES/OBJECTIVE:The purpose of this paper is to measure the exact angle of lateral crura with fixed reference points on the face. METHODS:We drew and marked LLC contours and vertical/horizontal lines in 40 consecutive rhinoplasty cases. We then divided them into two groups: (1) bulbous pinch and (2) flat LLCs. The right- and left-sided LLC angles to midline and horizontal lines were measured and compared to assess whether there was any significant difference between the two subgroups. RESULTS:There was no significant difference between the angles of LLC rotation in the bulbous and flat LLCs groups, measured both vertically and horizontally. CONCLUSION/CONCLUSIONS:Based on our findings, although cephalic malposition of LLCs may be present in some patients but in the majority of cases the etiology of nasal lateral wall pinching is not cephalic displacement of lateral crura but most probably is due, rather, to severe convexity of the posterior and lateral crura. According to our findings, cephalic malposition is an uncommon anatomic variation of LLCs that has been reported at high frequency (60-70% of their rhinoplasty cases). This finding may help to correct this deformity into a normal anatomic configuration. LEVEL OF EVIDENCE IV/METHODS:This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
PMID: 29644419
ISSN: 1432-5241
CID: 5484192
Bilateral Keratoconus Induced by Secondary Hypothyroidism After Radioactive Iodine Therapy [Case Report]
Lee, Ramon; Hafezi, Farhad; Randleman, J Bradley
PURPOSE/OBJECTIVE:To present a case of new-onset, bilateral, rapidly progressive keratoconus induced by secondary hypothyroidism after radioactive iodine therapy during the sixth decade of life that was successfully treated with corneal cross-linking. METHODS:Case report and literature review. RESULTS:A 53-year-old woman with no ocular complaints but with a history of Graves' disease and thyrotoxicosis was treated with radioactive iodine therapy and oral levothyroxine for secondary acquired hypothyroidism 3 years prior. Initially, uncorrected distance visual acuity (UDVA) was 20/40 and corrected distance visual acuity (CDVA) was 20/25 in both eyes. Over the following 3 years, the patient developed worsening UDVA and CDVA, with increasing manifest astigmatism of greater than 7.00 diopters (D) in the right eye and 4.75 D in the left eye, with corneal thinning and focal steepening and was diagnosed as having bilateral progressive keratoconus. The patient underwent sequential corneal cross-linking with resultant postoperative CDVA of 20/20 and reduced maximum keratometry and manifest astigmatism in both eyes. The patient's thyroid levels were within normal limits throughout the clinical course. CONCLUSIONS:This case provides evidence of the relationship between keratoconus development and thyroid gland dysfunction. The pathophysiology of this relationship has yet to be completely elucidated, but elevated levels of thyroxine in the aqueous humor and tear film and thyroxine receptors in the cornea likely play a role. Screening topographies for patients with thyroid gland dysfunction may be of value for these higher risk patients. [J Refract Surg. 2018;34(5):351-353.].
PMID: 29738593
ISSN: 1081-597x
CID: 5484212
Accelerated Corneal Cross-Linking With Photoactivated Chromophore for Moderate Therapy-Resistant Infectious Keratitis
Knyazer, Boris; Krakauer, Yonit; Baumfeld, Yael; Lifshitz, Tova; Kling, Sabine; Hafezi, Farhad
PURPOSE/OBJECTIVE:To evaluate the effect of accelerated corneal cross-linking with photoactivated chromophore (PACK-CXL) as additional treatment for therapy-resistant infectious keratitis. METHODS:In this interventional cohort study, 20 patients (11 men and 9 women), aged 65.5 (interquartile range = 21.5-78.5) years, who were hospitalized for moderate-sized therapy-resistant bacterial corneal ulcers (11/20 microbiologically confirmed) were treated with hypoosmolar 0.1% riboflavin solution and Ultraviolet A (UVA) irradiation for 3 minutes at 30 mW/cm (5.4 J/cm) as additional therapy to standard antimicrobial treatment. RESULTS:We did not observe any adverse effects of accelerated PACK-CXL on the corneal stroma or limbus. The median ulcer size was 3.00 (2.63-4.50) mm, the median time to reepithelialization was 6.50 (5.00-18.0) days, and the mean hospitalization period was 8.5 ± 4.5 days. Tectonic keratoplasty became necessary in 1 patient (5%). CONCLUSIONS:Our results suggest that accelerated PACK-CXL may provide an antimicrobial effect similar to the 1 low-intensity, slow setting (30 minutes at 3 mW/cm) and may be used as additional treatment in moderate-sized therapy-resistant infectious keratitis.
PMID: 29300262
ISSN: 1536-4798
CID: 5484172
Intraoperative optical coherence tomography to evaluate the effect of the eyelid speculum on corneal pachymetry during accelerated corneal cross-linking (9 mW/cm2)
Ghaffari, R; Mortazavi, M; Anvari, P; Salamat Rad, A; Alipour, F; Hafezi, F; Asgari, S; Hashemi, H
PurposeTo investigate intraoperative anterior segment optical coherence tomography (AS-OCT) to compare pachymetry changes between two methods (group 1: speculum-on, group 2: speculum-off during riboflavin instillation stage) during corneal cross-linking /CXL) (9 mW/cm2 for 10 min) in keratoconic patients.MethodsIn this interventional case series, 11 eyes (11 patients) in group 1 and 14 eyes (14 patients) in group 2 were enrolled. Pachymetry measurements by spectral domain OCT was performed at baseline, after epithelial removal, after 30 min of imbibition with riboflavin, and after UV irradiation. Repeated measures analysis of variance was used to compare the trend of changes in different stages of the procedure within and between two groups.ResultsThe corneal thinnest pachymerty (CTP) at baseline, after epithelial removal, 30 min of riboflavin instillation, and irradiation was 469.8±26.5, 438.0±27.1, 354.3±28.4, 367.1±31.8 microns in group 1 and 463.2±25.1, 438.0±27.1, 421.6±54.0, 386.9±34.0 microns in group 2, respectively. Group 1 showed a significantly greater decrease in the corneal pachymetry (P<0.001) during riboflavin instillation, while in group 2 a greater decrease in CTP was observed during the UV irradiation phase (P=0.002).ConclusionsUsing the intraoperative OCT, the speculum-off group had a more stable corneal pachymetry during riboflavin instillation time. Despite this, the effect was not lasting throughout the procedure; significant changes were noted in the corneal pachymetry at the end of operation in both groups; further highlighting the limitations imposed by corneal stromal shrinkage using isotonic dextran containing riboflavin solution for CXL.
PMCID:5848283
PMID: 29171504
ISSN: 1476-5454
CID: 5518422
Epithelial remodeling after corneal crosslinking using higher fluence and accelerated treatment time
Haberman, Ilyse D; Lang, Paul Z; Broncano, Alvaro Fidalgo; Kim, Sang Woo; Hafezi, Farhad; Randleman, J Bradley
PURPOSE/OBJECTIVE:) and accelerated treatment time (4 minutes) in eyes with progressive keratoconus using spectral-domain optical coherence tomography (SD-OCT) and to correlate focal epithelial and focal anterior curvature changes. SETTING/METHODS:Academic medical center in the United States. DESIGN/METHODS:Prospective case series. METHODS:Patients had anterior segment SD-OCT (RTVue-100) with focal stromal and epithelial measurements and Scheimpflug imaging before and 1, 3, 6, and 12 months after accelerated CXL. RESULTS:Twenty-seven eyes from 20 patients were evaluated. Before the accelerated CXL, the epithelium was thinnest in the inferior inner and outer temporal regions, whereas at 12 months postoperatively, the epithelium was significantly thinned in multiple inferior and nasal regions by 1.1 to 3.2 μm (P < .05, all measurements), with no significant changes from 6 to 12 months. Epithelial thickness standard deviation across the central 6.0 mm was significantly reduced by 3 months (1.4 μm, P = .09) and remained stable at 12 months (P = .009). Change in epithelial thickness was poorly correlated to change in anterior curvature (r = -0.035). CONCLUSIONS:Significant epithelial remodeling occurred after accelerated CXL in eyes with progressive keratoconus, with improved regularity across the central 6.0 mm, by 6 months after treatment. There was poor correlation between focal epithelial thickness and anterior curvature changes, with wide variability between patients. Establishing the pattern of epithelial remodeling after CXL might help optimize future custom treatment protocols.
PMID: 29610026
ISSN: 1873-4502
CID: 3026002