Morphological and functional correlations in riboflavin UV A corneal collagen cross‐linking for keratoconus

Purpose: To investigate the correlations between corneal structural modifications assessed by in vivo corneal confocal microscopy with visual function [uncorrected visual acuity (UCVA), best spectacle‐corrected visual acuity (BSCVA)] and morphological data (corneal topography, pachymetry, elevation analysis) after riboflavin UV A corneal collagen cross‐linking (CXL) for the stabilization of progressive keratoconus. Methods: Forty‐four eyes with progressive keratoconus were enrolled in the Siena Eye Cross Study (prospective nonrandomized phase II open trial). All eyes underwent Riboflavin UV A CXL. Preoperative and postoperative evaluation comprised: UCVA, BSCVA, optical pachymetry (Visante OCT, Zeiss, Germany), corneal topography (CSO, Florence, Italy) and tomography (Orbscan IIz; B&L, Rochester, NY, USA) and in vivo confocal microscopy (Heidelberg Retina Tomograph II; Rostock, Heidelberg Gmbh, Germany). Examinations were performed preoperatively 6 months and one day before treatment and at 1, 3, 6 and 12 months of follow‐up. Results: In vivo corneal confocal microscopy showed time‐dependent postoperative epithelial and stromal modifications after cross‐linking. Epithelial thinning associated with stromal oedema and keratocytes apoptosis explained initial tendency towards slightly reduced VA and more glare one month postoperatively in 70% of eyes. Furthermore, a statistically not significant early worsening of topographic mean K values was observed. Orbscan II analysis significantly underestimated pachymetric values after treatment. Pachymetric underestimation was rectified by high‐resolution optical pachymetry provided by the Visante OCT system. After the third post‐CXL month, epithelial thickening, disappearance of oedema and new collagen compaction recorded by in vivo corneal confocal microscopy explained the improvements in visual performance during the follow‐up. Changes in stromal reflectivity and collagen compaction observed by in vivo confocal microscopy were associated with corneal flattening and reduction in anterior elevation values recorded by differential topographic analysis. Conclusion: Corneal structural changes assessed by in vivo corneal confocal microscopy demonstrated significant correlations with visual function (UCVA and BSCVA) and morphological (corneal topography, pachymetry, elevation analysis) findings recorded after riboflavin‐UV A‐induced CXL.     

Long‐term biomechanical properties of rabbit cornea after photodynamic collagen crosslinking

Purpose: Photodynamic riboflavin/ultraviolet‐A (UVA)‐induced collagen cross‐linking, which increases the biomechanical stiffness of the human cornea by about 300%, has been introduced recently as a possible treatment for progressive keratoconus. The present study was undertaken to evaluate the longterm biomechanical effects of this new cross‐linking treatment as a necessary prerequisite to its clinical success. Methods: The corneas of the left eyes of nine male rabbits were cross‐linked. The contralateral eyes served as controls. After removal of the central 7 mm of the epithelium, the corneas were treated with the photosensitizer riboflavin and UVA irradiation for 30 mins with an irradiance of 3 mW/cm² using a 370‐nm UVA double diode. Groups of three animals were killed immediately after treatment and at 3 and 8 months, respectively. Biomechanical stress–strain measurements were performed using a microcomputer‐controlled biomaterial tester on 4 × 10‐mm corneal strips. Results: Corneal thickness in the treated rabbit cornea was 408 ± 20 μm. A constant and significant increase in ultimate stress (of 69.7–106.0%), Young’s modulus of elasticity (of 78.4–87.4%) and a decrease in ultimate strain (of 0.57–78.4%) were found over a time period of up to 8 months after cross‐linking treatment. Conclusions: Riboflavin/UVA‐induced collagen cross‐linking leads to a longterm increase in biomechanical rigidity which remains stable over time. These data support our previous longterm clinical observations and give hope that this new treatment will halt progressive keratoconus definitively.     

Transepithelial corneal collagen cross‐linking by iontophoresis of riboflavin

Purpose: To evaluate the effectiveness of transepithelial cornea impregnation with riboflavin 0.1% by iontophoresis for collagen cross‐linking. Material and methods:  Transepithelial collagen cross‐linking by iontophoresis of riboflavin was performed in a series of 22 eyes of 19 patients with progressive keratoconus I–II of Amsler classification. The riboflavin solution was administered by iontophoresis for 10 min in total, after which standard surface UVA irradiation (370 nm, 3 mW/cm²) was performed at a 5‐cm distance for 30 min. Results:  The riboflavin/UVA treatment resulted in a decrease in the average keratometry level from 46.47 ± 1.03 to 44.12 ± 1.12 D 1 year after the procedure. Corneal astigmatism decreased from 3.44 ± 0.48 to 2.95 ± 0.23 D. Uncorrected distance visual acuity improved from 0.61 ± 0.44 up to 0.48 ± 0.41 (LogMAR). Preoperative and postoperative endothelial cell density remained unchanged at 2765 ± 21.15 cells/mm². Conclusion:  Transepithelial collagen cross‐linking by iontophoresis might become an effective method for riboflavin impregnation of the corneal stroma reducing the duration of the procedure and being more comfortable for the patients. Further long‐term studies are necessary to complete the evaluation of the efficacy and risk spectrum of the modified cross‐linking technique.     

Silicone hydrogel mini‐scleral contact lenses in early stage after corneal collagen cross‐linking for keratoconus: a retrospective case series

Background : The aim was to the evaluate performance of a novel silicone hydrogel mini‐scleral contact lens (SHmS) for optical correction of keratoconus in the early stages after the corneal collagen cross‐linking procedure (CXL). Methods : We retrospectively analysed the visual acuity improvement and corneal adaptation in the first 10 eyes of nine patients fitted with SHmS lenses one to 3.5 months after corneal collagen cross‐linking. The lenses were designed to rest over the patients’ sclera and peri‐limbal cornea and vault the central cornea with minimal support over it. Visual acuities with manifest refraction and contact lenses, refractive and topographical values (Kmin and Kmax) were evaluated on lens dispensing and after six month of lens wearing. Ocular physiological responses were evaluated using the Institute of Eye Research (IER) grading scales. Results : SHmS fitting was performed 2.1 ± 0.97 (SD) months after collagen cross‐linking. Mean follow up was 10.9 ± 4.41 months (range six to 18 months). Mean decimal visual acuity with SHmS was 0.66 ± 0.22 (approximately 6/9 Snellen fraction, range 0.3 to 0.1) or 0.75 ± 0.14 (approximately 6/8.1, range 0.5 to 1.0), when omitting two amblyopic eyes. Nine (90 per cent) eyes were successfully fitted, that is, able to wear the lenses for 10 hours per day or longer. Mean wearing time was 11.7 hours (range six to 14) per day. No corneal neovascularisation or papillary reaction was found in all fitted eyes. Conclusions : SHmS contact lenses provide successful visual rehabilitation shortly after corneal collagen cross‐linking. This new soft contact lens design with scleral fixation and minimal apical touch was demonstrated to be safe shortly after collagen cross‐linking, as the avoidance of contact with the treated zone minimises contact lens influence on corneal recovery.     

Corneal cross‐linking – a review

Purpose

To review cross‐linking the cornea using riboflavin and ultraviolet A light, which has been widely adopted, refined and applied in a range of corneal surgeries and pathologies where the strength of the cornea might be compromised.

Recent findings

A large number of clinical trials have been carried out, most of which have demonstrated that standard cross‐linking is a successful method to halt the progression of keratoconus or even aid regression.

Summary

This review describes our current understanding of the technique, focussing on how cross‐linking works, how the treatment is being optimised, the clinical results that have been reported to date and the potential use of the therapy in the treatment of other corneal disorders.     

Collagen cross‐linking: a new treatment paradigm in corneal disease – a review

The last 2 years has seen a marked increase in the prominence of corneal collagen cross‐linking as a treatment strategy for progressive keratoconus. This interest has arisen from a body of laboratory evidence documenting the biomechanical and cellular changes induced by cross‐linking. The findings of this research provide a plausible rationale for its use in keratoconus to retard the progression of this common disease. The rapidly growing number of clinical reports suggests, not only a consistent stabilizing effect of cross‐linking, but that a variable improvement in corneal shape and visual function may also occur in some patients. However, the marked variation in the clinical course of keratoconus, together with the challenges of accurately evaluating refractive error, visual acuity and even corneal shape in this condition, demands further evidence from randomized controlled clinical trials. The aim of this review is to summarize the theoretical basis and risks of corneal collagen cross‐linking, along with the available evidence for its use in keratoconus and other corneal disease states.     

In vivo confocal laser-scanning microscopy to characterize wound repair in rabbit corneas after collagen cross-linking

Background: Collagen cross‐linking using the photosensitizer riboflavin combined with ultraviolet A light was developed to stiffen the cornea by increasing its mechanical and biochemical stability. Investigation of post‐treatment events, such as wound healing, is important to evaluate possible risks and to optimize treatment protocols. This in vivo confocal laser‐scanning microscopy study in rabbits was conducted to provide a quantitative and qualitative analysis of corneal wound repair over 16 weeks following collagen cross‐linking. Methods: Six New Zealand White rabbits underwent riboflavin/ultraviolet A cross‐linking. In vivo confocal laser‐scanning microscopy using a Heidelberg Retina Tomograph equipped with a Rostock Cornea Module was performed preoperatively and at 2, 4, 8, 12 and 16 weeks postoperatively. Results: From 2 weeks onwards the epithelium demonstrated no abnormalities. Evidence of inflammation was visualized in the intermediate, basal cells and Bowman's membrane. Nerve fibre regeneration was first noted at 12 weeks. Keratocyte activation and hyperreflective extracellular matrix were observed consistently, but by 16 weeks keratocyte activation was diminished, and extracellular matrix resumed normal reflectivity. Cell density in the posterior stroma and endothelium regained preoperative values by 4 weeks, although anterior stroma keratocyte cell density was still reduced by about 10% at 16 weeks. Conclusions: Complete qualitative and quantitative characterization of corneal wound repair was achieved by in vivo confocal laser‐scanning microscopy over 16 weeks following collagen cross‐linking in rabbits. In terms of assessing the ever‐increasing range of cross‐linking protocols, in vivo confocal laser‐scanning microscopy may contribute to minimizing the number of experimental animals, because multiple examinations of the same cases are possible over time.     

Effects of riboflavin/UVA corneal cross‐linking on keratocytes and collagen fibres in human cornea

Purpose: To evaluate the effects of corneal cross‐linking on keratocytes and collagen fibres in human corneas. Methods: Fifteen corneal buttons were examined. Ten were from patients with keratoconus submitted to penetrating keratoplasty and five of them were treated with cross‐linking 6 months before penetrating keratoplasty. Five normal corneal buttons from healthy donors were used as controls. All samples were prepared for TUNEL assay and Western blot analysis for the detection of keratocyte apoptosis and immunohistochemical analysis for the morphological evaluation of keratocytes and collagen fibre diameter. Results: Normal corneas exhibited no TUNEL‐positive keratocytes and keratoconic and cross‐linked corneas showed moderate apoptotic cells mainly in the anterior part of the stroma. This apoptotic trend was confirmed by the cleavage of poly (ADP‐ribose) polymerase assessed using Western blot. The Ki‐67 staining showed a significant increase in the keratocyte proliferation in cross‐linked corneas compared with normal and keratoconus. In cross‐linked corneas CD34‐positive keratocytes were regularly distributed throughout the whole corneal stroma as in the control, and keratoconus was associated with patchy loss of immunoreactivity. The immunohistochemical analysis of collagen type I showed a significant increase in fibre diameter of cross‐linked corneas compared with control and keratoconus. Conclusion: Corneal cross‐linking leads to keratocyte damage; after 6 months a repopulation by proliferating cells, a distribution of CD34‐positive keratocytes as in control and an increase in collagen fibre diameter were observed. These modifications are the morphological correlate of the process leading to an increase in biomechanical stability.     

Delayed neovascularization in inflammation‐induced corneal neovascularization in interleukin‐10‐deficient mice

Purpose: To investigate the potential modulatory role of interleukin‐10 (IL‐10) in the suture model for corneal neovascularization. Methods: Neovascularized areas were measured on corneal flat‐mounts in IL‐10^?/? and wild‐type C57BL6 mice. The inflammatory cellular response was characterized with immunohistochemistry. Gene expression was measured by real‐time polymerase chain reaction. Results: IL‐10^?/? mice showed a delayed neovascular response compared to wild‐type animals at day 6 after suture, when approximately half of the cornea was neovascularized. No apparent differences in inflammatory responses or in messenger RNA (mRNA) expression for proangiogenic factors were detected in IL‐10^?/? versus wild‐type mice. Conclusion: IL‐10 appears to have a proangiogenic effect in the suture model for corneal neovascularization that cannot be explained by either IL‐10’s anti‐inflammatory effect or apparent cross‐talk with the angiogenic factors vascular endothelial growth factor (VEGF)‐A, metalloproteinase (MMP)‐2 and MMP‐9, angiopoietin (Ang)‐1 and Ang‐2.     

The critical Dk/L to avoid oedema for daily wear RGP contact lenses

Background : A study was conducted to investigate the critical Dk/L required to avoid open-eye oedema with rigid gas-permeable (RGP) contact lenses. Methods : RGP contact lenses in matched designs were fabricated from three materials of nominal Dk of 12, 30 and 45 times 10^?11 (cm².mlO₂)/(s.ml.mmHg), with a centre thickness of 0.15 mm. A randomised, double-masked study design was used. Over two lens-wearing sessions one week apart, nine young adult subjects wore one lens made of each of the three materials for four hours. In one session the non-lens-wearing eye served as a control. Corneal thickness was measured using an ultrasonic pachometer before and after lens wear and the extent of corneal oedema calculated. Results : Lenses with a Dk/L of 8 times 10^?9 (cm.mlO₂)/(s.ml.mmHg) induced statistically significant levels of corneal oedema (1.8 ± 1.5 per cent) after four hours of open-eye wear. No corneal oedema was detected with lenses above this critical Dk/L value. No evidence could be found to support the concept of ‘osmotic’ corneal oedema induced by reflex lacrimation in unadapted subjects. Conclusion : RGP lenses with a Dk/L of 20 times 10^?9 (cm.mlO₂)/(s.ml.mmHg) or greater worn for daily wear are unlikely to induce corneal oedema in the majority of patients.     

Retinal artery occlusion following intravitreal anti‐VEGF therapy

Purpose: Anti‐vascular endothelial growth factor (anti‐VEGF) therapy effectively inhibits angiogenesis and is now enjoying widespread use in the treatment of age‐related macular degeneration (AMD). It may also have a role in the treatment of macular oedema secondary to other conditions. VEGF is a signalling molecule that has a variety of roles, including vasoregulation and effects on the coagulation homeostasis. Anti‐VEGF therapy may therefore have adverse effects on ocular blood flow. Methods: Two cases of retinal artery occlusion after intravitreal injection of anti‐VEGF are presented. Both patients were given the treatment to reduce macular oedema secondary to central retinal vein occlusion. Possible mechanisms are discussed. Results: Patient 1 developed a central retinal artery occlusion within 1 month of an intravitreal injection of ranibizumab (Lucentis^®). The macular oedema was totally resolved at 1 month; final visual acuity (VA) was light perception. Patient 2 developed a branch retinal artery occlusion in the macula 2 days after an intravitreal injection of bevacizumab (Avastin^®). The macular oedema was almost resolved within 1 week and did not recur; final VA was 0.6. Conclusions: Anti‐VEGF therapy may have a role in the treatment of macular oedema caused by central retinal vein occlusions. However, our report indicates that the therapeutic principle may be associated with an increased risk of retinal arterial occlusions.     

Corneal oxygenation during contact lens wear: comparison of diffusion and EOP‐based flux models

Purpose : The aim of this study was to compare corneal oxygen flux values derived from an oxygen diffusion model, with estimates from a model in which equivalent oxygen percentage (EOP) values were substituted for the post‐lens tear film oxygen tension in Fick's law. Methods : A previously described five‐layer corneal oxygen diffusion model was found to artefactually allow theoretical oxygen consumption, when the predicted oxygen tension fell to zero. Consequently, an eight‐layer diffusion model was constructed, with consumption set to zero at points within the cornea, where predicted oxygen tension falls to zero. Post‐lens tear layer thickness was corrected to more contemporary estimates. The eight‐layer and EOP‐based anterior corneal oxygen flux estimates were compared across the range of commonly encountered contact lens Dk/t values. Results : The eight‐layer model overcomes deficiencies in the five‐layer model and provides predicted values that are remarkably similar to the EOP‐based model. Open and closed eye anterior corneal oxygen flux in the absence of contact lens wear was estimated at 7.8 and 7.6 μL/cm²/hr for the open eye and 6.0 and 6.1 μL/cm²/hr for closed eye for the diffusion and EOP‐based models, respectively. Conclusions : The diffusion model supports the EOP model in that there is minimal oxygen benefit to be gained by increasing Dk/t above the Holden‐Mertz criteria of 24 and 87 times 10^?9 (cm/sec) (ml0₂/ml.mmHg) during open and closed eye wear, respectively. The eight‐layer model is suitable for further definition of corneal oxygenation during contact lens wear.     

角膜胶原交联术的远期效果

角膜胶原交联术(corneal collagen cross linking,CXL)是目前治疗角膜扩张性疾病的有效手段,经典去上皮技术长期效果肯定,但手术时间长,部分患者存在并发症.为提高安全性,CXL技术在不断改良,包括经上皮胶原交联、强紫外线光快速交联等.但这些改良CXL长期有效性尚存争议.去上皮胶原交联仍是目前最有效的胶原交联术式,目前报道的经上皮胶原交联及快速胶原交联的效果良好,但远期效果有待进一步随访研究.     

Contact lens management of keratoconus

Contact lenses are the primary form of visual correction for patients with keratoconus. Contemporary advances in contact lens designs and materials have significantly expanded the available fitting options for patients with corneal ectasia. Furthermore, imaging technology, such as corneal topography and anterior segment optical coherence tomography, can be applied to both gain insight into corneal microstructural changes and to guide contact lens fitting. This paper provides a comprehensive review of the range of contact lens modalities, including soft lenses, hybrid designs, rigid lenses, piggyback configurations, corneo‐scleral, mini‐scleral and scleral lenses that are currently available for the optical management of keratoconus. The review also discusses the importance of monitoring for disease progression in patients with keratoconus, in particular children, who tend to undergo more rapid progressive changes, so as to facilitate appropriate modification to contact lens fitting and/or potential referral for corneal collagen cross‐linking treatment, as appropriate.     

Dry‐eye syndrome after allogeneic stem‐cell transplantation in children

Purpose: To report the prevalence of dry‐eye syndrome (DES) in children and young adults treated with allogeneic stem‐cell transplantation (SCT) during childhood; to relate DES to conditioning regimes, including total body irradiation (TBI) and chemotherapy, and to immunosuppressive drugs and graft‐versus‐host disease (GVHD). Methods: This cross‐sectional study included 60 children/young adults transplanted because of leukaemia, various haematological disorders and inborn errors of metabolism between 1986 and 2004, with a follow‐up time of 7.0 years (median, range 2–18). Clinical assessments, performed at a median age of 15.6 years (range 5.5–23.5), included an inquiry form on dry‐eye symptoms, corneal status including fluorescein staining, ‘break‐up time’ (BUT) and Schirmer test. Results: A total of 37 of 60 patients had DES defined as presence of corneal epithelial lesions with a pathological BUT and/or Schirmer test. Twenty‐nine had had staining <1–10% of the corneal surface while eight patients had staining ≥10–25% of the corneal surface. All 37 patients with objective signs of DES, graded and not graded, had significant associations to subjective symptoms of dry eyes including dry eyes, red eyes, ocular irritation, secretion and sensitivity to light. Frequent occasions (above median; n = 7) of high cyclosporine A trough levels above 250 ng/ml were associated significantly with DES (P = 0.002). However, there was no association between DES and conditioning with single‐dose (s‐TBI) or fractionated TBI (f‐TBI), busulfan or other chemotherapy. There were no associations between prolonged corticosteroid treatment or chronic GVHD and DES in the present study. DES was more common in patients with malignant diseases (P = 0.02). Malignant disease increased the risk of DES in girls but not in boys. Increased age at SCT increased the risk for DES in boys but not in girls (P = 0.02). Although severe keratitis occurred in three patients, nobody suffered corneal perforation. Conclusion: DES with epithelial punctata keratopathy was common in children/young adults treated with SCT and more common if the patients were exposed to repeated high trough levels of cyclosporine A; however, DES was not associated with irradiation, corticosteroids or GVHD in the present study. Patients with objective DES also had subjective symptoms of dry eyes, which facilitate diagnosis. Girls with malignant diseases and boys who underwent SCT at later ages seem to demand higher attention and more frequent check‐ups regarding DES. Patients with diagnosed severe DES needed frequent and continuous ophthalmological care to maintain treatment motivation.     

Bone marrow cells and CD117‐positive haematopoietic stem cells promote corneal wound healing

Purpose: The present study was conducted to evaluate the therapeutic effects of topically applied bone marrow (BM) cells and CD117‐positive haematopoietic stem (CD117⁺) cells on alkali‐induced corneal ulcers. Methods: Bone marrow cells and CD117⁺ cells were isolated from syngenic mice and labelled with an intracellular cell tracer. Defined corneal wounds were produced in 89 eyes of syngenic mice and allowed to partially heal in vivo for 6 hr. The alkali‐burned eyes were enucleated 6 hr postinjury and randomly divided into three groups. Control group (33 eyes) was incubated with medium only. The treatment groups received either BM cells (30 eyes) or CD117⁺ cells (26 eyes) suspended in medium. Re‐epithelialization process of corneal defects was qualitatively and quantitatively assessed and statistically analysed. The corneas were examined by histological and immunohistochemical methods. Results: We found that the re‐epithelialization of corneal wounds in both treatment groups was significantly accelerated as compared to the control group. During the follow‐up period (85 hr), the corneal transparency was comparable in all groups. Morphological investigations of corneas from control and treatment group showed no evident differences in the phenotype of the regenerated epithelium. Additionally, corneas in the treatment groups were devoid of donor‐derived BM cells and CD117⁺ cells, respectively. Conclusions: This study provides evidence that topical application of BM cells or CD117⁺ cells can be used to reconstruct corneal surfaces. Because neither BM cells nor CD117⁺ cells were integrated into the corneal epithelium, we suggest that soluble factors could be responsible for the positive effect of BM cells and CD117⁺ cells on corneal wound healing.     

Soft‐shell technique using Viscoat® and Healon®5: a prospective,randomized comparison between a dispersive‐viscoadaptive and a dispersive‐cohesive soft‐shell technique

Purpose: To compare the efficacy of the dispersive‐viscoadaptive soft‐shell technique using Viscoat^® and Healon^®5 to the dispersive‐cohesive soft‐shell technique in reducing corneal endothelial cell damage during cataract surgery. Methods: In this prospective randomized study, 207 eyes of 171 cataract patients underwent phacoemulsification using the dispersive‐viscoadaptive soft‐shell technique (V‐group, 102 eyes) with Viscoat and Healon5 or the dispersive‐cohesive soft‐shell technique (C‐group, 105 eyes) with Viscoat and a cohesive agent (Opegan‐Hi^®). Each group was divided into two subgroups depending on the amount of ultrasound (%Min) used during phacoemulsification. Corneal endothelial cell density was examined preoperatively and 3 months postoperatively. The endothelial cell loss was compared between the two groups, and also between the subgroups. Results: The mean endothelial cell loss 3 months after surgery was 8.4 ± 5.6% standard deviation (SD) in the V‐group and 8.2 ± 6.2% in the C‐group (P = 0.787). In the subgroups with ultrasound of 10 %Min or less, the mean endothelial cell loss 3 months after surgery was 6.6 ± 4.6% in the V‐group and 5.5 ± 5.0% in the C‐group (P = 0.104). In the subgroups with ultrasound of over 10 %Min, this value was 10.6 ± 6.3% in the V‐group and 11.9 ± 5.7% in the C‐group (P = 0.413). The correlation coefficient of the endothelial cell loss rate and %Min was 0.245 (P = 0.0129) in the V‐group and 0.501 (P < 0.0001) in the C‐group. Conclusion: The dispersive‐viscoadaptive soft‐shell technique is as effective as the dispersive‐cohesive soft‐shell technique in protecting corneal endothelial cells during phacoemulsification regardless of the amount of ultrasound energy used.     

Long‐term follow up of autologous serum treatment for recurrent corneal erosions

Purpose: The aim of the study was to evaluate long‐term results of autologous serum treatment for recurrent corneal erosions. Methods: In this prospective single‐centre study, 33 eyes of 33 patients (21 male and 12 female) were treated with autologous serum eye drops for recurrent corneal erosions. Mean age of the patients was 49.3 ± 9.8 standard deviation (range 24–73) years. All subjects had failed to respond to other treatments. Autologous serum drops were administered for a 6‐month period: six times daily for the first 3 months and four times daily for the remaining 3 months. Detailed informed consent was obtained from the entire patient group before the study. Results: The mean follow‐up period was 30 ± 6.3 standard deviation (range 12–48) months. None of the patients experienced a recurrence while under treatment. Twenty‐eight patients (85%) had complete healing of erosions with no relapses of the disease over the whole follow‐up period. Five patients (15%) presented a single recurrence 3–12 months after the end of the treatment. No sight‐threatening complications were reported over the follow up. There was no statistically significant difference in the best spectacle‐corrected visual acuity values (t_stat = 2.1, F = 0.096, degree of freedom = 40 166, P < 0.41) or in the intraocular pressure measurements (P < 0.38) between the pre‐ and post‐treatment patient groups. Conclusions: Autologous serum drops proved to be a safe and efficient treatment modality for patients with recurrent corneal erosion syndrome as observed through a long‐term follow up.     

Conjunctival and corneal findings in bleb‐associated endophthalmitis: an in vivo confocal microscopy study

Purpose: To report the conjunctival and corneal findings in delayed onset glaucoma filtering bleb‐associated endophthalmitis (BAE), by using in vivo confocal microscopy (IVCM). Methods: This was an observational case series. Four eyes of four glaucomatous patients who previously underwent mytomicin C augmented filtering surgery and affected with delayed onset BAE, underwent IVCM of conjunctival bleb and cornea at diagnosis, after 2 and 8 weeks of therapy. The inflammatory status of the conjunctival epithelium and sub‐epithelium was microscopically investigated. Corneal epithelial cells, stromal and endothelial morphology were also evaluated. A group of eight patients with functioning conjunctival filtering bleb was used as control. Results: At diagnosis, a diffuse inflammatory cell infiltration within the conjunctival epithelium presenting evident microcysts was found; conversely, there were no such alterations in the sub‐epithelium. An evident stromal oedema, keratocytes activation and diffuse endothelial inflammatory precipitates were the major corneal hallmarks. After 2 weeks of therapy, besides a remarkable improvement of epithelial inflammation and an evident reduction in endothelial precipitates, dendritic cells appeared within conjunctival sub‐epithelium and corneal epithelium showed aspects of cellular disruption. After 8 weeks, the conjunctival and corneal features consistently improved, except for the endothelium which still presented high‐reflective residual precipitates. Conclusions: In vivo confocal microscopy proved valuable in the analysis of conjunctival bleb and cornea in patients affected with delayed onset BAE, permitting an evaluation of the course of the disease, the response to therapy and the modulation of dose regimen.     

Corneal Cross Linking for Keratoconus

Riboflavin-induced ultraviolet light (UV) cross linking has received a significant amount of attention in recent years. It is currently approved in Europe as a treatment for keratoconus and is also being used for other corneal disorders. The goal of this paper is to review in detail seminal papers and studies that have been done to support cross linking as a safe and effective treatment for patients with early stages of keratoconus.