Vito Romano

Transepithelial Iontophoresis Corneal Collagen Cross-linking for Progressive Keratoconus: Initial Clinical Outcomes

PURPOSE To report initial clinical results of transepithelial corneal collagen cross-linking with iontophoresis (I-CXL). METHODS Twenty eyes of 20 patients diagnosed as having progressive keratoconus who underwent I-CXL were included in this prospective non-randomized clinical study. Corrected distance visual acuity (CDVA), spherical equivalent and cylinder refraction, various corneal topography and Scheimpflug tomography parameters, aberrometry, anterior segment optical coherence tomography, and endothelial cell count were assessed at baseline and at 1, 3, 6, and 12 months postoperatively. RESULTS CDVA improved significantly at 3, 6, and 12 months postoperatively (logMAR difference of -0.07 ± 0.01, -0.09 ± 0.03, and -0.12 ± 0.06, respectively; P < .05). Aberrometry remained stable during follow-up and a trend toward improvement was noted. All topographic parameters (including maximum keratometry) were stable during the follow-up, but exhibited a positive non-significant trend toward improvement. Minimum corneal thickness values were stable for up to 12 months postoperatively. None of the patients showed a progression of keratoconus. Endothelial cell counts did not change significantly (P > .05). CONCLUSIONS Preliminary results up to 1 year postoperatively indicate the efficacy of I-CXL in stabilizing the progression of this degenerative disease combined with significant improvement of CDVA. I-CXL, which spares the corneal epithelium, has the potential to become a valid alternative for halting the progression of keratoconus while reducing postoperative patient pain, risk of infection, and treatment time in select patients; however, the relative efficacy of this technique compared to standard epithelium-off techniques remains to be determined.

Erratum to “Sterile Endophthalmitis after Intravitreal Injections”

In the original paper there is a missing Acknowledgment section, and it should include the following phrase: this paper has been partially funded by Instituto de Salud Carlos III, Project EC08/00192.

Sterile Endophthalmitis after Intravitreal Injections

Sterile endophthalmitis appears as an infrequent complication of intravitreal injections and seems to develop mainly in the context of the off-label use of drugs that have not been conceived for intravitreous administration. The aetiology of sterile endophthalmitis, independently of the administered drug, remains uncertain and a multifactorial origin cannot be discarded. Sterile inflammation secondary both to intravitreal triamcinolone acetonide and to intravitreal bevacizumab share many characteristics such as the acute and painless vision loss present in the big majority of the cases. Dense vitreous opacity is a common factor, while anterior segment inflammation appears to be mild to moderate. In eyes with sterile endophthalmitis, visual acuity improves progressively as the intraocular inflammation reduces without any specific treatment. If by any chance the ophthalmologist is not convinced by the sterile origin of the inflammation, this complication must be treated as an acute endophthalmitis because of the devastating visual prognosis of this intraocular infection in the absence of therapy.

Corneal Angiography for Guiding and Evaluating Fine-Needle Diathermy Treatment of Corneal Neovascularization

PURPOSE To investigate the outcome of selective occlusion of the afferent vessel of corneal neovascular complexes (CoNVs), using angiographically guided fine-needle diathermy (FND). DESIGN Retrospective interventional case series. SUBJECTS Patients with CoNV unresponsive to topical steroid therapy. METHODS Visual acuity, color images, and fluorescein angiography and indocyanine green angiography were measured before and after FND with a minimum of 3 months of follow-up. The number of afferent vessels crossing the limbus, time to fluorescein leakage, area, and geometric properties of the CoNV were determined using an in-house automated program written in numerical computing language (MatLab R14; The MathWorks Inc., Natick, MA). The location of the afferent vessel was identified from the angiographic images and marked at the slit lamp using a needle to make a cut to the depth of the vessel. We then applied FND using an electrolysis needle. MAIN OUTCOME MEASURES Area of CoNV. RESULTS Thirty patients underwent FND for CoNV that had not responded to treatment with topical steroids. The CoNV was associated with previous microbial keratitis (n = 26), intrastromal corneal ring segments (n = 2), ectodermal dysplasia (n = 1), and corneal choristoma (n = 1). Duration of CoNV was >6 months in 23 patients (77%), between 3 and 6 months in 3 patients (10%), and <3 months in 5 patients (13%). The number of afferent vessels per CoNV ranged from 1 to 3, with a mean diameter of 40 μm (standard deviation [SD], 10 μm) and mean time to leakage from apical vessels was 44.22 seconds (minimum, 27.43 seconds; maximum, 63.59 seconds). The number of FND treatments that were required was 1 for 20 patients (66.6%), 2 for 8 patients (26.6%), and 3 for 2 patients (6.6%). After FND, the area of CoNV reduced by 1.80 mm(2) (SD, 1.40 mm(2)), from 2.42 (SD, 1.59) to 0.62 mm(2) (SD, 0.73 mm(2)) up to 12 weeks postoperatively (P < 0.01). CONCLUSIONS The differentiation of afferent and efferent vessels using corneal angiography enables treatment to be selectively applied to the afferent vessels; there are usually 1 to 2 for each CoNV complex.

Influence of graft size on graft survival following Descemet stripping automated endothelial keratoplasty

Purpose To evaluate graft size on outcome following Descemet stripping automated endothelial keratoplasty (DSAEK) Methods Consecutive patients who had undergone a DSAEK for Fuchs endothelial dystrophy (FED) and pseudophakic bullous keratopathy (PBK) with at least 1 year of follow-up. Patients were divided into three groups according to the size of the donor trephine: <9, 9 and 9.5 mm. Main outcomes were postoperative best corrected visual acuity (BCVA) and graft failure. Grafts were prepared using an automated microkeratome. For larger grafts (≥9 mm), a manual dissection of the residual peripheral ring of anterior lamella was performed before trephination. Donor age, endothelial cell density (ECD) and postmortem times; recipient details including risk factors, comorbidity, surgical complications and postoperative BCVA and graft survival were analysed. Results Of 174 patients, 131 were included: 84 (64%) with FED and 47 (36%) with PBK. Mean preoperative and postoperative BCVA were 1.01±0.76 and 0.2±0.2 logMAR, respectively, at 12 months with 80.5% achieving 20/40 or better. Postoperative BCVA was significantly associated with ECD (p=0.005), PBK or FED (p=0.004), risk factors (p=0.007) and comorbidity (p=0.016). Eleven patients (8.40%) experienced endothelial graft failure; 17.86% for <9 mm, 7.69% for 9 mm and 3.84% for 9.5 mm trephine sized grafts. Graft failure was significantly associated with ECD (p=0.039) and graft trephine size (p=0.04). Conclusions Larger grafts occupy a smaller chord length in the eye than the trephine size and are expected to provide 10%–20% more endothelial cells. Increased graft size and donor ECD is significantly associated with a reduced graft failure rate.

Imaging Mass Spectrometry by Matrix-Assisted Laser Desorption/Ionization and Stress-Strain Measurements in Iontophoresis Transepithelial Corneal Collagen Cross-Linking

Purpose. To compare biomechanical effect, riboflavin penetration and distribution in transepithelial corneal collagen cross-linking with iontophoresis (I-CXL), with standard cross linking (S-CXL) and current transepithelial protocol (TE-CXL). Materials and Methods. The study was divided into two different sections, considering, respectively, rabbit and human cadaver corneas. In both sections corneas were divided according to imbibition protocols and irradiation power. Imaging mass spectrometry by matrix-assisted laser desorption/ionization (MALDI-IMS) and stress-strain measurements were used. Forty-eight rabbit and twelve human cadaver corneas were evaluated. Results. MALDI-IMS showed a deep riboflavin penetration throughout the corneal layers with I-CXL, with a roughly lower concentration in the deepest layers when compared to S-CXL, whereas with TE-CXL penetration was considerably less. In rabbits, there was a significant increase (by 71.9% and P = 0.05) in corneal rigidity after I-CXL, when compared to controls. In humans, corneal rigidity increase was not significantly different among the subgroups. Conclusions. In rabbits, I-CXL induced a significant increase in corneal stiffness as well as better riboflavin penetration when compared to controls and TE-CXL but not to S-CXL. Stress-strain in human corneas did not show significant differences among techniques, possibly because of the small sample size of groups. In conclusion, I-CXL could be a valid alternative to S-CXL for riboflavin delivery in CXL, preserving the epithelium.

Corneal oedema and its medical treatment

Corneal oedema is a common sign of acute or protracted corneal disease of various aetiologies. In this paper, we review the causes and pathophysiological bases of corneal oedema, as well as discussing the goals and modalities of its medical treatment. Corneal oedema, if adequately understood and appropriately treated, generally shows a good prognosis.

Corneal Indocyanine Green Angiography to Guide Medical and Surgical Management of Corneal Neovascularization.

Purpose: To illustrate the role of corneal angiography in the clinical assessment and surgical treatment of patients with complex corneal neovascularization (CoNV). Methods: A case series of 3 patients with CoNV is presented whose management was guided by indocyanine green (ICG) and fluorescein corneal angiography. In the first case, there was recurrent lipid exudation into an intrastromal cleft from CoNV; in the second, there was progressive exudation from CoNV at the graft–host interface; in the third, CoNV was associated with rejection after deep anterior lamellar keratoplasty. Results: In the first case, angiography helped to identify and treat the feeder vessels and stop further leakage. In the second case, it was possible using angiography to differentiate CoNV arising from iris and limbal vasculature enabling angiographic-guided fine-needle diathermy with cessation of exudation. In the third case, angiography revealed the location of CoNV in the host–graft interface after deep anterior lamellar keratoplasty, rather than within the corneal stroma. Conclusions: Corneal angiography is a useful diagnostic tool to guide medical and surgical management of CoNV by enabling the localization of vessel depth and topography.

A COL17A1 splice-altering mutation is prevalent in inherited recurrent corneal erosions

PURPOSE Corneal dystrophies are a genetically heterogeneous group of disorders. We previously described a family with an autosomal dominant epithelial recurrent erosion dystrophy (ERED). We aimed to identify the underlying genetic cause of ERED in this family and 3 additional ERED families. We sought to characterize the potential function of the candidate genes using the human and zebrafish cornea. DESIGN Case series study of 4 white families with a similar ERED. An experimental study was performed on human and zebrafish tissue to examine the putative biological function of candidate genes. PARTICIPANTS Four ERED families, including 28 affected and 17 unaffected individuals. METHODS HumanLinkage-12 arrays (Illumina, San Diego, CA) were used to genotype 17 family members. Next-generation exome sequencing was performed on an uncle-niece pair. Segregation of potential causative mutations was confirmed using Sanger sequencing. Protein expression was determined using immunohistochemistry in human and zebrafish cornea. Gene expression in zebrafish was assessed using whole-mount in situ hybridization. Morpholino-induced transient gene knockdown was performed in zebrafish embryos. MAIN OUTCOME MEASURES Linkage microarray, exome analysis, DNA sequence analysis, immunohistochemistry, in situ hybridization, and morpholino-induced genetic knockdown results. RESULTS Linkage microarray analysis identified a candidate region on chromosome chr10:12,576,562-112,763,135, and exploration of exome sequencing data identified 8 putative pathogenic variants in this linkage region. Two variants segregated in 06NZ-TRB1 with ERED: COL17A1 c.3156C→T and DNAJC9 c.334G→A. The COL17A1 c.3156C→T variant segregated in all 4 ERED families. We showed biologically relevant expression of these proteins in human cornea. Both proteins are expressed in the cornea of zebrafish embryos and adults. Zebrafish lacking Col17a1a and Dnajc9 during development show no gross corneal phenotype. CONCLUSIONS The COL17A1 c.3156C→T variant is the likely causative mutation in our recurrent corneal erosion families, and its presence in 4 independent families suggests that it is prevalent in ERED. This same COL17A1 c.3156C→T variant recently was identified in a separate pedigree with ERED. Our study expands the phenotypic spectrum of COL17A1 disease from autosomal recessive epidermolysis bullosa to autosomal dominant ERED and identifies COL17A1 as a key protein in maintaining integrity of the corneal epithelium.

Macular Hypotrophy After Internal Limiting Membrane Removal For Diabetic Macular Edema

Purpose: To compare the anatomic and functional effects of three different approaches to nontractional diabetic macular edema. Methods: Retrospective comparative study. Sixty eyes of 60 patients diagnosed with cystoid diabetic macular edema and treated with 1.25 mg/mL intravitreal bevacizumab (Group A), laser photocoagulation (Group B), or vitrectomy with inner limiting membrane peeling (Group C) were included in the study. Changes in number of Early Treatment Diabetic Retinopathy Study letters, central macular thickness, largest diameter of the intraretinal cysts (IC), and choroidal thickness were investigated. Analyses were performed during follow-up visits at Months 1, 3, 6, 9, and 12. Results: Visual acuity only significantly improved in Group A at the last follow-up (P = 0.004). Central macular thickness significantly decreased in every group throughout the follow-up period. Differences in central macular thickness between Groups A and B (P < 0.01), A and C (P < 0.01), and B and C (P < 0.01) were significant. Intraretinal cysts also significantly decreased in each group throughout the follow-up period. Differences in IC size between Groups A and B (P = 0.8), A and C (P = 0.1), and B and C (P = 0.1) were not significant. Choroidal thickness did not undergo any significant change in any group throughout the follow-up period. A significant correlation was also found in Group A between best-corrected visual acuity at month 12 and baseline central macular thickness (R = 0.3; P = 0.006), and in Group B between postoperative best-corrected visual acuity at month 12 and baseline IC size (R = 0.8; P < 0.01, negatively correlated at 92.4%). Conclusion: According to our retrospective data, diabetic macular edema with intraretinal cysts larger than 390 &mgr;m should not be treated with vitrectomy with ILM peeling, because this may induce subfoveal atrophy, defined as the “Floor Effect,” and subsequent visual deterioration.