Corneal Haze Formation Research Articles

Effect of Prophylactic Mitomycin C on Corneal Endothelium Following Transepithelial Photorefractive Keratectomy in Myopic Patients.

PurposeThis study investigated the effect of prophylactic mitomycin C (MMC) on corneal endothelium to inhibit corneal haze formation post transepithelial photorefractive keratectomy (T-PRK).MethodsA total of 120 eyes of 60 patients with low, moderate, and high myopia were subjected to T-PRK with intraoperative application of MMC (0.02%) for 30–50s. Patients’ files were categorized into three groups according to ablation depths (if ≥100 µm) during T-PRK as follows: (1) Group A – low myopia without MMC, (2) Group B – low myopia with MMC, and (3) Group C – moderate/high myopia with MMC. Preoperative/surgical parameters and refractive outcomes were documented. Cell density (CD), number of cells (NUM), coefficient of variation, central corneal thickness (CCT), hexagonality (HEX/6A), average cell area (AVG), and its standard deviation (SD) were evaluated using specular microscopy preoperatively and postoperatively.ResultsOverall, 119 out of 120 eyes showed significant prevention of corneal haze. Groups A and C showed no significant changes in endothelial CD and NUM. Group B showed a non-significant reduction in CD. However, all three groups showed significant variations in HEX/6A, CCT, AVG, and SD.ConclusionThe MMC application did not significantly affect corneal endothelial density or number and can be used safely and effectively to prevent corneal haze following T-PRK in myopia.

Treatment of Keratoconus with WaveLight Contoura and Corneal Cross-Linking Combined.

PurposeTo investigate the outcomes of the treatment of keratoconus/corneal ectasia utilizing topographic-guided ablation (WaveLight Contoura) followed by corneal cross-linking.MethodsThirty-six eyes of 21 patients were treated for keratoconus/corneal ectasia utilizing topographic guided ablation photorefractive keratectomy (PRK) for treatment of corneal higher-order aberrations and refractive error followed immediately by 15-minute cross-linking were examined retrospectively. Six-month results were analyzed via measurement of vision, refraction, residual higher-order aberrations (HOAs), residual lower-order and higher-order aberrations, as well as for loss or gains of lines of best-corrected visual acuity.ResultsAll eyes save one had reduction in K1, K2, K Max, K Mean. All eyes had reduction in manifest astigmatism, Contoura-measured astigmatism, higher-order aberrations, higher-order aberrations grouped with lower-order aberrations (Grouped). Four eyes had lost 1–2 lines of vision, mainly to corneal haze formation, 17 eyes gained lines of vision, and 15 eyes equaled their pre-op best-corrected visual acuity. Eight eyes from four sample patients have their data included in this manuscript to demonstrate the procedure and the outcomes.ConclusionTreatment with WaveLight Contoura combined with 15-minute corneal cross-linking is an effective and safe treatment for keratoconus and should be considered a primary treatment to prevent corneal transplant as well as improve vision and corneal irregularity.

Safety profiles of terahertz scanning in ophthalmology

Terahertz (THz) technology has emerged recently as a potential novel imaging modality in biomedical fields, including ophthalmology. However, the ocular biological responses after THz electromagnetic exposure have not been investigated. We conducted a rabbit study to evaluate the safety profiles of THz scanning on eyes, at a tissue, cellular, structural and functional level. Eight animals (16 eyes) were analysed after excessive THz exposure (control, 1 h, 4 h, and 1 week after continuous 4-h exposure; THz frequency = 0.3 THz with continuous pulse generated at 40 µW). We found that at all the time points, the corneas and lens remained clear with no corneal haze or lens opacity formation clinically and histopathologically. No thermal effect, assessed by thermographer, was observed. The rod and cone cell-mediated electroretinography responses were not significantly altered, and the corneal keratocytes activity as well as endothelial viability, assessed by in-vivo confocal microscopy, was not affected. Post-exposed corneas, lens and retinas exhibited no significant changes in the mRNA expression of heat shock protein (HSP)90AB1), DNA damage inducible transcript 3 (DDIT3), and early growth response (EGR)1. These tissues were also negative for the inflammatory (CD11b), fibrotic (fibronectin and α-smooth muscle actin), stress (HSP-47) and apoptotic (TUNEL assay) responses on the immunohistochemical analyses. The optical transmittance of corneas did not change significantly, and the inter-fibrillar distances of the corneal stroma evaluated with transmission electron microscopy were not significantly altered after THz exposure. These results provide the basis for future research work on the development of THz imaging system for its application in ophthalmology.

Mitomycin C application after photorefractive keratectomy in high, moderate, or low myopia: Systematic review and meta-analysis.

Photorefractive keratectomy (PRK) is considered a safe approach laser procedure with a clinical significance in correcting myopia results. PRK requires removing the whole superficial epithelium. The integrity of the epithelial basement membrane and the deposition of abnormal extracellular matrix can put the cornea in a probable situation for corneal haze formation. Mitomycin C (MMC) is applied after excimer laser ablation as a primary modulator for wound healing, limiting corneal haze formation. We aim to summarize the outcomes of MMC application after laser ablation. We searched Scopus, PubMed, Cochrane CENTRAL, and Web of Science till December 2020 using relevant keywords. The data were extracted and pooled as mean difference (MD) or risk ratio (RR) with a 95% confidence interval (CI), using Review Manager software (version 5.4). Our analysis demonstrated a statistically significant result for MMC application over the control group in terms of corneal haze formation postoperatively (RR = 0.29, 95% CI: [0.19, 0.45], P < 0.00001). Regarding corrected distance visual acuity (CDVA), no significant difference was observed between the MMC group and the control group (MD = 0.02; 95% CI: [-0.04, 0.07]; P = 0.56). Regarding the uncorrected distance visual acuity (UDVA), the analysis favored the MMC application with (MD -0.03, 95% CI: [-0.06, -0.00]; P = 0.05). There was no statistically significant increase in complications with MMC. In conclusion, MMC application after PRK is associated with a lower incidence of corneal haze formation with no statistically significant side effects. The long term effect can show improvement regarding UDVA favoring MMC. However, there is no significant effect of MMCs application regarding CDVA, and SE.

Development and Optimization of Freeze-Dried Eye Drops Derived From Plasma Rich in Growth Factors Technology.

PurposeTo investigate whether plasma rich in growth factors (PRGF) eye drops maintain their biological potential after a freeze drying process. The addition of a lyoprotectant like trehalose was also evaluated.MethodsBlood from three healthy donors was collected to obtain eye drops by PRGF technology. The resultant eye drops were divided in four groups: PRGF, freeze-dried PRGF (PRGF lyo), and PRGF lyophilized mixed with 2,5% trehalose (PRGF lyo+2.5T) or 5% trehalose (PRGF lyof+5T). Chemical and biological characteristics were evaluated. Photorefractive keratectomy was performed on C57BL/6 mice which were divided in three treatment groups: control, PRGF, and PRGF lyo. Corneal wound healing and haze formation were evaluated macroscopically. Eyes were collected at 1, 2, 3, and 7 days after surgery, and were processed for histologic studies.ResultsThe pH values of PRGF samples increased significantly after the lyophilization process. Osmolarity levels increased significantly in PRGF samples mixed with trehalose in comparison with PRGF samples without protectants. The freeze drying process maintained growth factors levels as well as the biological properties of PRGF eye drops even without the use of lyoprotectants. PRGF lyo treatment significantly decreased the re-epithelialization time and haze formation in photorefractive keratectomy-treated corneas regarding PRGF and control groups. Furthermore, the PRGF lyo group significantly decreased the number of smooth muscle actin-positive cells in comparison with the control group at each time of the study and at days 2 and 3 in the PRGF group.ConclusionsThe freeze drying process preserves the protein and growth factor content as well as the biological properties of PRGF eye drops, even without the use of protectants. Freeze-dried PRGF eye drops accelerate corneal tissue regeneration after photorefractive keratectomy in comparison with the control group.Translational RelevanceOur study shows the feasibility to preserve the biological capability of PRGF eye drops as freeze-dried formulation, avoiding the addition of protectants.

Phototherapeutic keratectomy

Phototherapeutic keratectomy is an excimer laser–based surgical procedure widely performed by corneal surgeons for treating anterior corneal stromal pathologies. Phototherapeutic keratectomy helps by ablating the corneal stroma, thereby improving corneal clarity and smoothening the surface. Transient discomfort and induced hyperopia from corneal flattening are the immediate postoperative concerns. The long-term course is often marked by the recurrence of original corneal pathology and corneal haze formation. Phototherapeutic keratectomy, however, allows for repeat stromal ablation for managing recurrences, as the corneal thickness permits, without affecting the outcome of future keratoplasty. Adjunctive methods such as topical mitomycin-C may be additionally used to reduce recurrence rates. Also, various masking agents such as carboxymethyl cellulose, sodium hyaluronate, and dextran are used in eyes with irregular corneal surface to allow for uniform stromal ablation. Overall, phototherapeutic keratectomy has provided corneal surgeons an additional surgical tool, particularly those residing in developing nations where the availability of donor corneal tissue is an important limiting factor.

A comparative, randomized, contralateral study between the use of Mitomycin-C and accelerated cross-linking as adjuvant therapy after trans-epithelial all surface laser ablation for moderate to high myopia (ASLA-MMC vs. ASLA-XTRA): a pilot study

ABSTRACTObjectives: The purpose of our study is to compare accelerated corneal cross-linking (CXL) against topical application of Mitomycin-C (MMC), in patients undergoing all-surface laser ablation (ASLA) for moderate-to-high myopia and/or myopic astigmatism contralaterally and evaluate the efficacy of this technique in the prevention of postoperative corneal haze formation as well as the efficacy of refractive results.Methods: This prospective study consisted of 34 eyes of 17 myopic (range: −4.00 to −10.5 D, SD: 2.11) patients (8 males, 9 females). Mean age was 26.88 years (SD: 6.04, range: 19–36 years). One eye was randomly selected to ASLA with MMC while the contralateral eye underwent ASLA with accelerated CXL.Results: There was no statistically significant difference in the UDVA between the two groups at all postoperative time intervals (1,3,6, and 12 months). The keratometric values of the eyes and the haze score showed no statistically difference between the two groups at any time point.Conclusion: ASLA combined with accelerated CXL(ASLA-XTRA) appears to be a safe alternative to the use of MMC as an adjuvant treatment in moderate and high myopia. The potential additional benefits of this modality are the stabilizing effect of the refractive result and its sterilization effect on the treated cornea.

MiR-145 Is a Promising Therapeutic Target to Prevent Cornea Scarring.

Corneal scarring is an expected outcome of corneal injury or infection and is one of the major causes for visual loss. The formation of light-scattering myofibroblasts is thought to be the underlying cause of corneal haze formation. Recently, microRNA (miRNA) gene therapies have been proposed as novel approach for complex processes such as fibrosis and scarring. In this study, we focused on the role of miR-145 in corneal myofibroblast differentiation and function. Analysis of human corneal scar tissue and transforming growth factor (TGF)-β1-induced corneal myofibroblasts showed a 13- and 4-fold increase of miR-145, respectively, compared with healthy cornea and nonstimulated fibroblasts (p<0.01). Furthermore, myofibroblasts showed an increase in α-smooth muscle actin (α-SMA) expression and a decreased expression of Kruppel-like factor 4 (KLF4). These results indicated that TGF-β1 increases miR-145 expression, which indirectly induces α-SMA expression via downregulation of KLF4, a known negative regulator of α-SMA. Consistently, miR-145 silencing in corneal myofibroblasts using a specific antimiR resulted in increased KLF4 and strongly decreased α-SMA expression. In addition, miR-145 inhibition also significantly decreased myofibroblast contractility, migratory capacity, and TGF-β1 secretion, which are all thought to contribute to corneal scarring. Hence, miR-145 plays an important role in TGF-β1-stimulated corneal myofibroblast differentiation and activation, which can be reversed by miR-145 silencing. Therefore, we suggest miR-145 as a promising therapeutic target for miRNA-based gene therapy to prevent or treat visual loss caused by corneal fibrosis.

Assessment of anti-scarring therapies in ex vivo organ cultured rabbit corneas

The effects of a triple combination of siRNAs targeting key scarring genes were assessed using an ex vivo organ culture model of excimer ablated rabbit corneas. The central 6 mm diameter region of fresh rabbit globes was ablated to a depth of 155 microns with an excimer laser. Corneas were excised, cultured at the air–liquid interface in defined culture medium supplemented with transforming growth factor beta 1 (TGFB1), and treated with either 1% prednisolone acetate or with 22.5 μM cationic nanoparticles complexed with a triple combination of siRNAs (NP-siRNA) targeting TGFB1, TGFB Receptor (TGFBR2) and connective tissue growth factor (CTGF). Scar formation was measured using image analysis of digital images and levels of smooth muscle actin (SMA) were assessed in ablated region of corneas using qRT-PCR and immunostaining. Ex vivo cultured corneas developed intense haze-like scar in the wounded areas and levels of mRNAs for pro-fibrotic genes were significantly elevated 3–8 fold in wounded tissue compared to unablated corneas. Treatment with NP-siRNA or steroid significantly reduced quantitative haze levels by 55% and 68%, respectively, and reduced SMA mRNA and immunohistostaining. This ex vivo corneal culture system reproduced key molecular patterns of corneal scarring and haze formation generated in rabbits. Treatment with NP-siRNAs targeting key scarring genes or an anti-inflammatory steroid reduced corneal haze and SMA mRNA and protein.

The U.S. Army Surface Ablation Study: Comparison of PRK, MMC-PRK, and LASEK in Moderate to High Myopia

To compare visual outcomes following photorefractive keratectomy (PRK), PRK with mitomycin C (MMC-PRK), and LASEK in moderate and high myopia in military personnel. This prospective, randomized contralateral eye study included 167 patients 21 years or older with manifest spherical equivalent -5.99 ± 1.40 diopters (D) (range: -3.88 to -9.38 D) randomized to either MMC-PRK or LASEK treatment in their dominant eye and conventional PRK without MMC in the fellow eye. All procedures were performed using the LADARVision 4000 Excimer Laser System (Alcon Surgical Inc., Ft. Worth, TX). High- and low-contrast visual acuities, manifest refraction, endothelial cell count, and corneal haze were evaluated up to 12 months postoperatively. At 12 months postoperatively, visual outcomes were comparable among the treatment groups. Corneal haze of any grade was less common in MMC-PRK compared to PRK at 1 month (21.4% vs 31.0%; P < .01) and 3 months (12.8% vs 35.9%; P = .03) postoperatively; it was also less common in MMC-PRK compared to LASEK at 1 month (21.4% vs 55.9%; P < .01), 3 months (12.8% vs 42.4%; P < .01), and 6 months (12.2% vs 36.4%; P = .03) postoperatively. Haze rate (grade 0.5 or higher) was comparable between LASEK and PRK. Clinically significant haze (grade 2 or higher) developed after PRK (4 eyes) and LASEK (2 eyes), but not after MMC-PRK. MMC-PRK showed some benefits in minimizing corneal haze formation. One year after surgery, there was no discernible difference in the postoperative refractive outcomes among the three methods.

In Vivo Evaluation of a Decellularized Limbal Graft for Limbal Reconstruction

Corneal and limbal epithelial function is highly dependent on its underlying matrix. In this study, we report the in vitro and in vivo effects of a decellularized limbal matrix on corneal and limbal epithelial differentiation and repair. We demonstrate that a limbal matrix helps to maintain epithelial cells in a more proliferative and less differentiated state. We introduce a novel focal injury model to the limbus using an excimer laser and further show that transplanting a decellularized limbal graft after the limbal injury helps to promote epithelialization and reduce corneal haze formation. These results suggest that a decellularized limbal graft may be therapeutically beneficial in clinical cases of focal limbal deficiency.

Corneal Collagen Fibril Changes After Ultraviolet A/Riboflavin Corneal Crosslinking

The aim was to investigate the changes in collagen type 1 and type 3 in rabbit corneas undergoing corneal crosslinking with ultraviolet A and riboflavin and to analyze the possible mechanisms of corneal haze formation. After removal of the central epithelium, the right corneas of 60 New Zealand rabbits were crosslinked with riboflavin and ultraviolet A, and 10 additional rabbits were used as the control group. The animals were killed 3, 7, 15, 30, 90, and 180 days postoperatively. Collagen type 1 and type 3 were analyzed using picrosirius red stain by means of polarized light microscopy. The biochemical changes in collagen type 3 at the time points indicated above were determined by Western blot analyses. Collagen type 3 was significantly increased 30 days after corneal crosslinking compared with that in the control cornea, gradually increased until reaching its maximum value 90 days after riboflavin and ultraviolet A crosslinking, and then decreased until it returned to the normal state 180 days after crosslinking. There were no significant changes in collagen type 1 over time after corneal crosslinking. In agreement with the picrosirius red staining results, the western blot analyses showed that collagen type 3 was detected 15 days after the crosslinking treatment and continued to be present. However, 180 days after the crosslinking treatment, collagen type 3 could not be found in the crosslinked corneas. These findings suggest that ultraviolet A/riboflavin crosslinking results in collagen type 3 synthesis and degradation, which may offer at least a partial explanation for the formation of corneal haze.

Laser‐assisted subepithelial keratectomy versus epipolis laser in situ keratomileusis for myopia: a meta‐analysis of clinical outcomes

To identify possible differences between laser-assisted subepithelial keratectomy and epipolis laser in situ keratomileusis for myopia. Meta-analysis. Patients from previously reported comparative studies treated by laser-assisted subepithelial keratectomy versus epipolis laser in situ keratomileusis. A systematic literature retrieval was conducted in the MEDLINE, EMBASE and Cochrane Library, up to January 2013. The included studies were subject to a meta-analysis using a RevMan 5.1 version software. The differences in efficacy, predictability, safety, epithelial healing time, pain perception and corneal haze formation. A total of six studies involving 517 eyes were included. There were no statistically significant differences in the final proportion of eyes with uncorrected visual acuity of 6/6 or better (P = 0.43), mean postoperative uncorrected visual acuity (P = 0.53), final proportion of eyes with refraction within ± 0.50 D (P = 0.62) and ± 1.00 D (P = 0.16) of target, final proportion of eyes losing two or more lines of best spectacle-corrected visual acuity (P = 1.00), healing time of corneal epithelium (P = 0.58), final proportion of eyes with corneal haze grade 0.5 or higher (P = 0.26), and corneal haze levels (P = 0.36). There were no significant differences in efficacy, predictability, safety, epithelial healing time and corneal haze formation between laser-assisted subepithelial keratectomy and epipolis laser in situ keratomileusis, but the result was limited. Future more data are required to detect the potential differences between the two procedures.

Plasma rich in growth factors (PRGF-Endoret) stimulates corneal wound healing and reduces haze formation after PRK surgery

This study evaluated the efficacy of Plasma rich in growth factors (PRGF-Endoret) on the corneal wound healing process after Photorefractive keratectomy (PRK). To address this, blood from three healthy donors was collected, centrifuged and, the whole plasma column (WP) and the plasma fraction with the highest platelet concentration (F3) were collected. The effects of F3 and WP on the proliferation and migration of human corneal epithelial cells (HCE) were analyzed. PRK was performed on C57BL/6 mice. Animals were divided in three treatment groups: Control, F3, and WP. Corneal wound healing and haze formation were evaluated macroscopically. Eyes were collected at 1, 2, 3, and 7 days after surgery, and were processed for histological studies. Immunofluorescence was used to assess cellular proliferation, apoptosis and myofibroblast transformation in the mouse cornea. Results showed a significant increased on proliferation and wound healing after F3 and WP treatment when compared with control group. In vivo studies showed significant reduction on haze formation in mice treated with both PRGF-Endoret formulations (F3 and WP). Histological studies showed an increase of epithelial cell proliferation in corneas of control group, promoting an epithelial hyperplasia. The number of SMA-positive cells (corresponding to myofibroblast differentiation) was significantly lower in the PRGF-Endoret group than in the control group, correlating with the higher transparence results observed macroscopically in both PRGF-Endoret groups. According to this, it can be concluded that PRGF-Endoret accelerates corneal tissue regeneration after PRK, reducing haze formation.

Genomics of corneal wound healing: a review of the literature

Corneal wound healing is a complex process: its mechanisms and the underlying genetic control are not fully understood. It involves the integrated actions of multiple growth factors, cytokines and proteases produced by epithelial cells, stromal keratocytes, inflammatory cells and lacrimal gland cells. Following an epithelial insult, multiple cytokines are released triggering a cascade of events that leads to repair the epithelial defect and remodelling of the stroma to minimize the loss of transparency and function. In this review, we examine the literature surrounding the genomics of corneal wound healing with respect to the following topics: epithelial and stromal wound healing (including inhibition); corneal neovascularisation; the role of corneal nerves in wound healing; the endothelium; the role of aquaporins and aptamers. We also examine the effect of ectasia on corneal wound healing with regard to keratoconus and following corneal surgery. A better understanding of the cellular and molecular changes that occur during repair of corneal wounds will provide the opportunity to design treatments that selectively modulate key phases of the healing process resulting in scars that more closely resemble normal corneal architecture.

Comparison of TGF-β1 in tears and corneal haze following Epi-LASIK with and without mitomycin C.

To compare transforming growth factor-β1 (TGF-β1) levels in tears and the degree of corneal haze formation following epithelial laser in situ keratomileusis (Epi-LASIK) with and without the use of mitomycin C (MMC) and to investigate the effect of MMC on corneal wound healing. Thirty-two patients (64 eyes) with high myopia underwent Epi-LASIK surgery, and MMC was randomly used in one eye in each patient. The epithelialization process was observed, and the TGF-β1 level in tears was measured at 1 day, 3, and 7 days postoperatively for comparison with baseline. Corneal haze was graded at 1 month, 3, and 6 months after surgery. Mean preoperative spherical equivalent refraction was -8.24±2.18D (range -6.00 to -10.50D) in the MMC group and -7.82±1.55D (range -6.00 to -9.75D) in the non-MMC group. There was no significant difference between the two groups (P=0.38). Mean epithelialization time was (5.02±0.68) days in the MMC group and (4.86±0.57) days in the non-MMC group (P=0.31). Tear fluid TGF-β1 levels were similar before surgery (P=0.34), but were significantly higher in the non-MMC group at 1 day, 3, and 7 days postoperatively (P=0.004, 0.008, and 0.012, respectively). Corneal haze scores 1 month after surgery were significantly higher in the non-MMC group (P=0.03), and similar at 3 and 6 months after surgery (P=0.28 and 0.62, respectively). MMC did not delay epithelialization. In early postoperative period, lower TGF-β1 levels in tears and a lower grade of corneal haze were observed in the MMC group. Our findings suggest that the ability of MMC to inhibit Epi-LASIK-induced haze might be mediated through TGF-β1 suppression.

The role of topical vitamin A in promoting healing in surface refractive procedures: a prospective randomized controlled study

AimTo evaluate the effect of topical vitamin A supplementation on corneal re-epithelialization time, postoperative pain, visual acuity, and haze following photorefractive keratectomy (PRK).Patients and methodsThis prospective study included 32 patients. For each patient, one eye was randomized to the vitamin A group and the fellow eye to the non-vitamin A group (control group). Eyes in the vitamin A group received perioperative topical vitamin A (retinol palmitate, 250 IU/g VitAPOS eye ointment [AFT Pharmaceuticals Pty, Ltd, Sydney, NSW, Australia]) in addition to the classic treatment for PRK. Clinical outcomes were evaluated up to 3 months after PRK.ResultsThere was no difference in the mean time to complete healing between the vitamin A group and the control group (3.36 ± 0.6 days in the control group; 3.42 ± 0.7 days in the vitamin A group; P = 0.854). Mean postoperative pain at the 48-hour visit was 4.35 ± 1.42 over 10 in the control group, and 4.42 ± 1.37 over 10 in the vitamin A group, with no difference between the two groups (P = 0.589). Subepithelial haze evaluated at 3 months postoperatively did not differ between the two groups (P = 0.960). Also, visual and refractive outcomes were not different between the two groups 3 months postoperatively.ConclusionTopical vitamin A supplementation did not affect re-epithelialization time, postoperative pain, corneal haze formation, or visual outcomes after PRK.

Anterior Corneal Aberrations after Descemet's Stripping Endothelial Keratoplasty for Fuchs' Endothelial Dystrophy

To determine the change in anterior corneal high-order aberrations (HOAs) after Descemet's stripping endothelial keratoplasty (DSEK) for Fuchs' dystrophy, and to compare the HOAs with those of age-matched controls. Prospective cohort and cross-sectional study. Forty-eight eyes with Fuchs' dystrophy were examined before and after DSEK, and were compared with 52 eyes of age-matched controls with normal corneas. Corneas of patients with Fuchs' dystrophy were examined prospectively before and at intervals through 2 years after DSEK. Wavefront errors from the anterior corneal surface were derived from corneal topograms and were expressed as Zernike polynomials through the sixth order. Best-corrected visual acuity (BCVA) was measured by the electronic Early Treatment of Diabetic Retinopathy Study protocol, and subepithelial haze was measured from the brightness of confocal images. Total HOAs were compared before and after DSEK, and with those of age-matched controls, by using generalized estimating equation models. Relationships between HOAs, BCVA, subepithelial haze, and recipient age were determined. Anterior corneal HOAs, BCVA, and subepithelial haze (backscattered light). In Fuchs' dystrophy before DSEK, total HOAs (4 mm optical zone) from the anterior corneal surface (0.29±0.13 μm) were higher than those of controls (0.17±0.08 μm; P<0.001). At 2 years after DSEK, total HOAs (0.26±0.13 μm) did not differ from preoperative aberrations (P = 0.99), and remained higher than in controls (P<0.001). At 2 years, total HOAs were correlated with BCVA (r = 0.59; P<0.001; n = 27), with subepithelial haze (r = 0.41; P = 0.01; n = 25), and with recipient age (r = 0.59; P<0.001; n = 27). Anterior corneal HOAs are higher in Fuchs' dystrophy than in controls, and remain higher through 2 years after DSEK. The aberrated anterior surface might be related to anterior corneal ultrastructural changes and haze formation in Fuchs' dystrophy, and should not be ignored as a source of decreased visual acuity after DSEK.

Formaldehyde-induced keratopathy after strabismus surgery

We report on a patient who developed corneal haze and permanent ptosis after strabismus surgery. Formaldehyde-disinfected sodium hyaluronate which was used to protect the corneal epithelium during surgery was thought to have induced keratopathy and other findings. To our knowledge, this is the first report of corneal haze formation together with ptosis secondary to formaldehyde toxicity as a complication of strabismus surgery.

Pretranscriptional Regulation of Tgf-β1 by PI Polyamide Prevents Scarring and Accelerates Wound Healing of the Cornea After Exposure to Alkali

Corneal alkali burns are a serious clinical problem that often leads to permanent visual impairment. In this process, transforming growth factor (Tgf)-beta1 is upregulated and involved in the response to corneal injury and the process of corneal stromal scarring. To develop an efficient compound to inhibit Tgf-beta1 in the cornea, we designed GB1201, a pyrrole-imidazole (PI) polyamide targeting rat Tgf-beta1 gene promoter to the activator protein-1 (AP-1) binding site. GB1201 showed a high binding affinity to the target DNA sequence in the gel mobility shift and Biacore assays. GB1201 significantly inhibited the rat Tgf-beta1 gene promoter activity in HEK (human embryonic kidney) 293 cells in a concentration-dependent manner. Topically administrated GB1201 was distributed immediately to the nuclei of all cell layers of the cornea and remained for 24 hours. A corneal alkali burn model in rats was used to evaluate the therapeutic efficacy of GB1201. GB1201 suppressed the upregulation of Tgf-beta1 in the burned cornea, both in the mRNA and protein levels. Moreover, daily treatment with GB1201 for a week significantly improved the corneal tissue wound healing, reduced corneal stromal scarring, and prevented corneal haze formation. Our data suggest that PI polyamide may open new opportunities for therapeutic intervention in the treatment of chemically burned corneas.