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Corneal allograft survival is mediated by the variety of immunological reactions and wound healing process. Our aim was to explore the effects of topical administration of ripasudil, a selective Rho-associated coiled-coil protein kinase inhibitor, on corneal allograft survival. Ripasudil was administered to mice thrice a day after allogeneic corneal transplantation. Corneal graft survival, opacity, neovascularization, re-epithelization, immune cell infiltration, and mRNA levels of angiogenic and pro-inflammatory factors in the grafted cornea and draining lymph nodes (dLNs) were evaluated with slit-lamp microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction. Graft survival was significantly prolonged with lower graft opacity and neovascularization scores in 0.4% and 2.0% ripasudil-treated groups, and mRNA levels of angiogenic and pro-inflammatory factors in ripasudil-treated grafted corneas were reduced. Moreover, 0.4% and 2.0% ripasudil reduced CD45 + -infiltrated leukocyte frequency, Cd11b and Cd11c mRNA levels, and the frequencies of mature dendritic cells, IFNγ-, and IL-17- producing CD4 + T cells in the dLNs of recipients. Re-epithelization rate of the grafted cornea was significantly higher in the 0.4% and 2.0% ripasudil groups than in the control. Topically applied ripasudil prolonged graft survival by downregulating neovascularization and inflammation factors, while promoting corneal re-epithelization, suggesting that ripasudil may be useful for suppressing immunological rejection in corneal transplantation.

The purpose of this study was to compare central corneal thickness, thinnest corneal thickness, and the thinnest point of the cornea between Pentacam and anterior segment optical coherence tomography (ASOCT) in patients with dry eye disease (DED). This cross-sectional study included 195 participants between November 2015-June 2017. DED was diagnosed using the Asia Dry Eye Society criteria and further divided into mild and severe DED based on kerato-conjunctival vital staining. Central corneal thickness, thinnest corneal thickness, and the thinnest point of the cornea measured by Pentacam and ASOCT were compared, and Pearson's correlation coefficients were estimated. The differences in central corneal thickness and the thinnest corneal thickness between Pentacam and ASOCT were analysed using Bland-Altman and multivariate regression analyses adjusted for age and sex. This study included 70 non-DED subjects and 52 patients with mild and 73 with severe DED. The Pentacam and ASOCT measurements of central corneal thickness and thinnest corneal thickness were strongly correlated, but the respective values were higher when measured with Pentacam. The Bland-Altman analysis revealed differences in central corneal thickness (non DED, 11.8; mild DED, 13.2; severe DED, 19.6) and in thinnest corneal thickness (non DED, 13.1; mild DED, 13.4; severe DED, 20.7). After adjusting for age and sex, the differences in central corneal thickness (β = 7.029 μm, 95%CI 2.528-11.530) and thinnest corneal thickness (β = 6.958 μm, 95%CI 0.037-13.879) were significantly increased in the severe-DED group. The distribution of the thinnest point of the cornea in the cornea's inferior temporal quadrant between Pentacam and ASOCT deviated in severe DED (Pentacam: 90.4% vs. ASOCT: 83.6%). Clinicians should consider that there were significant differences in corneal-morphology assessment between the measurements with Pentacam and ASOCT in severe DED., Competing Interests: The authors have declared that no competing interests exist.

Purpose: We examined the wound-healing effect of retinol palmitate (VApal) on mucin gene and protein expressions in a rat dry eye model based on lacrimal gland (LG) resection after injury., Methods: The rat dry eye model was prepared by surgical resection of the main LG in male Long-Evans rats. After alkaline injury of the central part of the lower palpebral conjunctiva bilaterally, VApal eye drops at 1,500 IU/mL in one eye and a vehicle in the fellow eye were both administered 6 times a day for 7 days. The expression of mucin gene and protein was analyzed by real-time polymerase chain reaction or enzyme-linked immunosorbent assay in the cornea and conjunctiva of MUC1, MUC4, MUC16, and MUC5AC after 1, 3, (5), and 7 days of treatment with VApal., Results: Significant decreases in fluorescein-stained areas and rose bengal scores were observed in VApal-treated dry eyes compared with vehicle-treated dry eyes at both 3 (P < 0.05) and 7 days (P < 0.01). Significant increases in corneal rMuc4 and conjunctival rMuc5AC after 1 day (P < 0.01) and conjunctival rMuc16 gene expression after 3 days were observed with VApal treatment (P < 0.05). Furthermore, conjunctival MUC16 expression significantly increased after 3 days of VApal treatment (P < 0.05)., Conclusions: VApal promoted corneal rMuc4, conjunctival rMuc5AC, and conjunctival rMuc16 gene expression in a rat dry eye model after injury. VApal also promoted conjunctival MUC16 expression. These results indicate that VApal has efficacy in improving keratoconjunctival epithelial damage associated with decreased tear production.

Purpose: A national survey was conducted in Japan to analyze the clinical characteristics of pellucid marginal corneal degeneration (PMD)., Methods: A questionnaire was sent to all members of the Japan Cornea Society requesting demographic and clinical findings on PMD patients who had been examined between 2008 and 2010. The presence of band-shaped peripheral corneal thinning, detected by slit-lamp biomicroscopy or by a pachymetric map, was set as the diagnostic criterion of PMD., Results: Most of the participating facilities relied on either slit-lamp biomicroscopy or corneal topography as diagnostic tools for the detection of PMD. Data on 347 patients (579 eyes) were returned from the participating facilities for analysis, among which 162 eyes in 84 men and 24 women, with a median onset age of 37 years, met the PMD criteria. Of the 108 patients (162 eyes) with classical PMD, unilateral involvement was found in 25 % of patients (27 eyes). In 17 of the 27 eyes for which topographic findings for the contralateral eye were available, seven eyes were either keratoconus or had a suspected diagnosis of keratoconus. An association with allergic disease was found in 24 eyes (22.2 % of patients). Approximately half of the patients had 1.0 or better spectacle-corrected distance visual acuity, and only 5 % showed 0.1 or worse. The mean keratometric value was 45.7 diopters. On corneal topography, 100 eyes (61.7 %) showed the topographic "crab-claw pattern," and the remaining eyes showed other patterns, including inferior steepening (22.2 %) and an irregular pattern (10.5 %)., Conclusions: We conducted the largest clinical survey of PMD to date and found a male predominance, a relatively high prevalence of unilateral involvement, and associated allergic diseases.

Purpose: To evaluate the outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) using corneas from elderly donors., Methods: A total of 90 eyes that underwent DSAEK at Juntendo University Hospital between January 2008 and December 2012 were divided into two groups. Group 1 was eyes that received corneas from elderly donors aged 80 years or older (29 eyes), and group 2 was eyes that received corneas from donors aged 79 years or younger (61 eyes). Patient characteristics and visual acuity, endothelial cell density, and postoperative complications at 2 years after surgery were examined retrospectively., Results: The mean age of the donors was 86.3 ± 28.9 years (range, 80-98 years) in group 1 and 62.1 ± 23.2 years (range, 26-79 years) in group 2. At 2 years after surgery, median logMAR visual acuity was 0.48 ± 0.38 in group 1 and 0.42 ± 0.47 in group 2, while the median loss of endothelial cell density was 38.9 ± 22.5 % and 39.7 ± 23.8 %, respectively. There was no significant difference between the two groups for all the parameters., Conclusions: The rate of endothelial cell loss at 2 years after surgery was similar regardless of donor age (≥80 years vs ≤79 years). It seems reasonable to use corneas from donors aged 80 years or older for DSAEK provided the selection criteria are fulfilled.

Purpose: Our aim was to evaluate the surgical technique and postoperative results of Descemet stripping automated endothelial keratoplasty (DSAEK) for bullous keratopathy in eyes with microcornea., Methods: Two patients with microcornea (8.8 mm in case 1 and 9.3 mm in case 2) and bullous keratopathy after cataract surgery or after laser iridotomy were treated by DSAEK. A donor lamella with a smaller diameter (7.5 mm) was inserted into the anterior chamber using the double-glide donor insertion technique (Busin glide with intraocular lens sheet glide)., Results: No intraoperative or postoperative complications occurred. Corrected visual acuity improved from counting fingers to 0.222 logMAR in case 1 and from 1.000 to 0.155 logMAR in case 2 over 6 months. Corneal endothelial cell loss was 6.5 % in case 1 and 1.9 % in case 2., Conclusions: DSAEK was useful for bullous keratopathy in patients with microcornea. However, surgery should be done with meticulous care, and modification of the diameter of the donor lamella and of the donor insertion technique may be required.

A role of vitamin A in the synthesis of hyaluronic acid by skin cells is well known. Hyaluronic acid is produced by corneal epithelial cells and keratocytes in the eye. We investigated whether rabbit corneal epithelial cells and keratocytes release hyaluronic acid after exposure to vitamin A compounds. Rabbit corneal epithelial cells and keratocytes were inoculated with RCGM2 medium and incubated at 37ºC under 5% CO(2) in air for 24 h. The medium was then replaced with medium containing 0.1, 1, 10, or 100 μM retinoic acid or retinol palmitate (VApal) and incubated for another 48 h. Hyaluronic acid release from both corneal epithelial cells and keratocytes during culture was increased by retinoic acid at the lower concentration of 0.1 μM and 1 μM determined with a sandwich binding protein assay kit. However, it was significantly decreased at the higher concentrations of 10 μM and 100 μM, and the cell count determined with a Neutral Red assay kit was also decreased at these concentrations. On the other hand, hyaluronic acid release from corneal epithelial cells during culture was increased by VApal at the lower concentration of 0.1 μM and 1 μM, but there was no significant difference in the cell count for either corneal epithelial cells or keratocytes in the presence of VApal at any concentration. In conclusion, it is suggested that vitamin A stimulates the release of hyaluronic acid from cultured rabbit corneal epithelial cells and keratocytes.

Purpose: To investigate the effect of tacrolimus on chemokine production by corneal myofibroblasts compared with that of cyclosporine or dexamethasone., Methods: We investigated the expression of FK506-binding protein 12, calcineurin, and nuclear factor of activated T cells in corneal myofibroblasts by immunocytochemistry and flow cytometry. Next, we investigated whether toll-like receptor 9 ligand, CpG-DNA, or toll-like receptor 3 ligand, poly (I:C), induced the production of chemokines such as interleukin (IL) 8, Gro-α, and IL-6 by corneal myofibroblasts using enzyme-linked immunosorbent assay. Finally, we assessed the effect of tacrolimus on the production of these chemokines compared with that of cyclosporine or dexamethasone., Results: FK506-binding protein 12, calcineurin, and nuclear factor of activated T cells were constantly expressed by cultured corneal myofibroblasts. CpG DNA and poly (I:C) enhanced the production of IL-8, Gro-α, and IL-6 by corneal myofibroblasts. At a concentration 10 nM/L or higher, dexamethasone strongly inhibited the production of these chemokines. In contrast, cyclosporine concentrations of 10 ng/mL or more enhanced the production of these chemokines by cells stimulated with poly (I:C). On the other hand, tacrolimus (at 10 ng/mL or more) inhibited the production of these chemokines by corneal myofibroblasts stimulated with poly (I:C) but not with CpG-DNA., Conclusions: These results suggest that tacrolimus and dexamethasone, but not cyclosporine, have a direct immunosuppressive effect on corneal myofibroblasts. Therefore, when inflammatory diseases of the ocular surface are treated by tacrolimus, especially in combination with steroids, caution with regard to the risk of corneal infection may be needed.

The interaction of fibroblast growth factor-inducible 14 (Fn14) and, its ligand tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is known to be important in wound healing of tissues. However, to our knowledge, expression and function of Fn14 in corneal myofibroblasts, which have a crucial role in wound healing of corneal stroma, has not been investigated. In this study, we investigated the expression and function of Fn14 in corneal myofibroblasts. Expression of Fn14 protein was assessed by flow cytometry. Corneal myofibroblasts showed strong expression of Fn14 protein, while keratocytes did not. TGF-beta(1) promoted the differentiation of keratocytes into corneal myofibroblasts, and induced Fn14 expression. These data reveal that keratocytes phenotype determines the level of Fn14 expression. ELISA was used to detect chemokines and matrix metalloproteinases in the supernatant of corneal myofibroblasts cultured with or without stimulation by TWEAK and/or TGF-beta(1). TWEAK increased the production of IL-8, MCP-1, and RANTES by corneal myofibroblasts via Fn14. TGF-beta(1) augmented the TWEAK-induced production of these chemokines. TWEAK also increased the production of MMP-1 and -3 by corneal myofibroblasts via Fn14, while TGF-beta(1) inhibited this effect of TWEAK on MMP production. TWEAK-induced phosphorylation of NF-kappaB and MAP kinase in corneal myofibroblasts. Furthermore, TWEAK partially inhibited the differentiation of keratocytes into corneal myofibroblasts promoted by TGF-beta(1). These data suggest that the Fn14/TWEAK system may have several roles in wound healing by corneal myofibroblasts. In the future, modulation of the TWEAK/Fn14 system may become a novel approach for control corneal wound healing.

Purpose: In vivo study of corneal deposits in a patient receiving chlorpromazine therapy was done by using a confocal microscope, the HRT II Rostock corneal module (RCM)., Methods: A 23-year-old woman who had been on chlorpromazine therapy for 5 years complained of bilateral photophobia and was referred to our clinic. She had suffered from light sensitivity for 4 years., Results: Slit-lamp microscopy revealed white deposits, particularly in the layers of the endothelium and Descemet membrane, which were concentrated in the center of both corneas. Deposition of many white granules was observed in the superficial subepithelial stroma of the cornea by HRT II RCM. Granular deposits were observed at the center of most cells in the corneal endothelium., Conclusions: The HRT II RCM could clearly detect deposits in the corneal endothelium, as well as in other regions such as the corneal epithelium and stroma.

Purpose: To investigate the expression and function of toll-like receptor (TLR)-3 and -9 in corneal myofibroblasts., Methods: Two types of human keratocytes were used, which were freshly isolated keratocytes from donor corneas and cultured keratocytes. Expression of the mRNAs for various molecular markers was analyzed in these cells by RT-PCR, and TLR-2, -3, -4, and -9 mRNAs were also analyzed by RT-PCR. Expression of TLR-3 and -9 at the protein level was assessed by flow cytometry. In addition, an antibody array and ELISA were used to detect chemokines and cytokines in the supernatant of cultured keratocytes, with or without stimulation by poly inosine-polycytidylic acid (poly (I:C)) or CpG-DNA. Furthermore, a phagocytosis assay was performed to evaluate whether signaling via TLR-3 and -9 enhances phagocytosis., Results: Keratocytes cultured for three passages underwent differentiation into corneal myofibroblasts. TLR-3 and -9 were detected in corneal myofibroblasts at the mRNA and protein levels, but not in freshly isolated keratocytes. Stimulation of corneal myofibroblasts with poly (I:C) or CpG-DNA enhanced the production of IL-6, IL-8, GRO, ENA-78, and RANTES compared with that by untreated cells. Phagocytic activity of myofibroblasts was upregulated by signaling via TLR-3 and -9., Conclusions: This is the first report on the in vitro expression and function of TLR-3 and -9 in corneal myofibroblasts. The findings suggest that the keratocyte phenotype determines the expression of TLR-3 and -9 and that corneal myofibroblasts may have an important role in bacterial and viral clearance.

Bone marrow-derived cells (BMCs) reside in the anterior stroma of the central and paracentral cornea, as well as all stromal layers of the peripheral cornea, in normal human eyes. We investigated the factors regulating the constitutive distribution of BMCs in normal human corneal stroma. Cultured human corneal keratocytes expressed several chemokines (growth-related oncogene/CXCL1-3, IL-8/CXCL8, and MCP-1/CCL2) in the Ab array study. CCR2 and CCR7 mRNAs were detected in BMCs by multiplex RT-PCR. Keratocytes/corneal epithelial cells and BMCs selected from normal human donor corneas by using magnetic beads expressed MCP-1/CCL2 and CCR2 protein, respectively. BMCs isolated from human corneal stroma showed a chemotactic response to MCP-1/CCL2 in the Boyden chamber assay. The chemotactic effect of keratocyte supernatant was inhibited by blockade of MCP-1/CCL2. This is the first work on constitutive expression of CCR2 by BMCs from the corneal stroma and MCP-1/CCL2 by keratocytes/epithelial cells. Our findings suggest that the interaction between MCP-1/CCL2 and CCR2 determines the distribution of constitutive BMCs in normal human corneal stroma.

Purpose: To investigate the interaction and compatibility between a soft contact lens (SCL) and an ophthalmic drug., Methods: Samples were prepared with the nonionic SCL (groups I and II), the anionic SCL (group IV), and the zwitter ionic SCL (group IV). Chlorpheniramine maleate and sodium cromoglycate were used to measure the drug uptake into the SCL., Results: The results showed the largest drug uptake into the anionic SCL accompanied with dimensional changes and lower drug uptakes into the nonionic and the zwitter ionic SCL with dimensional stability. The cell permeability of the substances when instilled in the eye over the SCL was also measured. The zwitter ionic SCL allowed cell permeability comparable to that by oral administration., Conclusions: These results indicated the possibility for the zwitter ionic SCL as a lens to be worn concomitantly with ophthalmic drug instillation.

To determine normal corneal eccentricity in a rural Japanese population and to examine factors associated with eccentricity value. This used data from the Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS) project between 2009 and 2012. Residents of Minamiaizu and Tadami in Fukushima, Japan, who were aged 40 years or over, were invited for a comprehensive eye examination. For 1371 patients with no history of internal eye surgery, corneal eccentricity was measured using a Pentacam. Of 1371 people recruited to the study, 1215 (1215 eyes) met the inclusion criteria. The overall mean eccentricity was 0.46 (SD = 0.18; range, −0.85 to 0.88). Corneal eccentricity was significantly associated with age, spherical equivalent, pupil diameter, anterior chamber angle, anterior chamber volume, and central corneal thickness, but not with gender or body mass index. In this study, the normal cornea in this Japanese population was prolate. Corneal eccentricity was likely to decrease with increasing age. Also, spherical equivalent and other anterior segment parameters had an influence on corneal eccentricity. Corneal eccentricity measurements might be helpful in the diagnosis of corneal diseases and in calculations for intraocular lens implantation and corneal refractive surgery. [ABSTRACT FROM AUTHOR]

Purpose: Benzalkonium Chloride (BAK) is reported to have the potential to damage the cornea. We developed a composition with broad-spectrum antimicrobial activity without preservatives by combining trometamol, boric acid, and ethylenediaminetetraacetic acid (TBE). This study aimed at evaluating the corneal damage caused by TBE and comparing it with that caused by BAK. Methods: SV40-immortalized human corneal epithelial cell line (HCE-T) was treated with BAK or TBE, and the cell viability was measured. The exposure time that caused 50% cell death (CDT50) was calculated. Transepithelial electrical resistance (TEER) was measured before and after treatment with BAK or TBE. Occludin was detected with immunostaining and Western blotting after treatment with BAK or TBE. The effect of BAK or TBE on membrane-associated mucins was evaluated with rose bengal (RB) staining. Results: In the BAK group, cell viability decreased in a dose-dependent manner. The viability of the TBE group was significantly greater than that of the BAK group. The CDT50 of the TBE group is greater than that of the BAK groups. In the BAK groups, the recovery of TEER was delayed in a dose-dependent manner, whereas in the TBE group, the recovery occurred earlier. Localization of occludin was disrupted, and the amount of occludin was significantly reduced among the cells exposed to BAK. The area stained with RB in the BAK groups increased, whereas that in the TBE group did not increase. Conclusion: These results suggest that the application of TBE would be useful for developing preservative-free ophthalmic preparations that offer both sufficient safety and antimicrobial activity. [ABSTRACT FROM AUTHOR]

Purpose: We examined the efficacy of retinol palmitate (VApal) for dry eyes using dry eye model rabbits whose lacrimal glands were resected. Materials and methods: After alkaline injury on keratoconjunctival epithelium, VApal eye drops were administered 6 times a day for 7 days. The efficacy of VApal was also compared with that of 0.1% hyaluronic acid eye drops. Results: The fluorescein staining and rose bengal scores showed a significant decrease compared with the score in the vehicle group at 7 days (P < 0.05) in the 1000 IU/mL VApal group and at both 3 days (P < 0.05) and 7 days (P < 0.01) in the 1500 IU/mL VApal group. Histological examination revealed recovery of the corneal epithelium, and PAS staining disclosed the recovery of mucin-producing lower palpebral conjunctival goblet cells after 7 days in the 1500 IU/mL VApal group compared with the vehicle group. Results from impression cytology showed a significant increase in density of conjunctival goblet cells compared with that in the vehicle group after 7 days in the 1000 IU/mL VApal group and after 3 and 7 days in the 1500 IU/mL VApal group. There were no significant changes in tear flow in either group. Topical application of VApal at 1500 IU/mL showed greater improvement than 0.1% hyaluronic acid in both fluorescein and rose bengal score and in the density of conjunctival goblet cells. Conclusion: It is suggested that VApal is effective for the improvement of keratoconjunctival epithelial damage associated with tear abnormalities, such as dry eyes. [ABSTRACT FROM AUTHOR]

Purpose: Orthokeratology for correction of myopia reduces corneal power by flattening corneal curvature and thinning central corneal thickness (CCT). Measurement of intraocular pressure (IOP) with a noncontact tonometer is known to be affected by CCT and corneal curvature. We investigated the influence of orthokeratology on such measurements of IOP. Methods: This was a prospective, interventional case series derived from a clinical trial of orthokeratology lenses in two hospitals. Both eyes of 45 subjects were fitted with reverse-geometry lenses, worn for more than 4 h overnight for 52 weeks. Uncorrected visual acuity, refraction, IOP (with a noncontact tonometer), CCT, and corneal curvature were measured. Results: Uncorrected visual acuity, spherical equivalent value, IOP, CCT, and the radius of corneal curvature were 0.93 ± 0.27, −2.87 ± 1.05 D, 13.5 ± 2.5 mmHg, 536.2 ± 39.6 μm, and 7.88 ± 0.25 mm, respectively, before orthokeratology, and 0.17 ± 0.34, −1.05 ± 1.18 D, 12.4 ± 2.7 mmHg, 528.6 ± 40.8 μm, and 8.10 ± 0.31 mm at 52 weeks after treatment. The changes in all parameters were significant, and the change in IOP was significantly correlated with that in CCT at 24 weeks and thereafter. Conclusions: Orthokeratology for myopia leads to a decrease in IOP measured with a noncontact tonometer, likely as a result of the associated decrease in CCT. [ABSTRACT FROM AUTHOR]

Purpose: To compare the effect of three intracameral antibiotics, gentamicin (GM), gatifloxacin (GFLX), and moxifloxacin (MFLX), on the rabbit corneal endothelium. Methods: Twenty-four eyes from 18 rabbits were used. In the GM treatment group of 12 eyes, a dose of 20 mg/ml, 2 mg/ml, 200 μg/ml, or 20 μg/ml of GM was injected into the anterior chamber. In the GFLX and MFLX treatment groups were injected into the anterior chamber of three eyes. The central corneal thickness was measured. The eyes were then enucleated for observation under scanning electron microscopy. Results: Three days after the intracameral injection, a significant difference in central corneal thickness was found between the GM 20 mg/ml group and the control group ( P < 0.05), but not between any other groups. The damage rate at the endothelial cell level was 67% in the GM 20 mg/ml group, 56% in the GM 2 mg/ml group, 33% in the GM 200 μg/ml group, 22% in the GM 20 μg/ml group, 22% in the GFLX group, and 0% in the MFLX group. Conclusions: Intracameral GFLX or MFLX was almost nontoxic to the rabbit corneal endothelium, in contrast to the toxic results of intracameral GM 20 and 2 mg/ml. [ABSTRACT FROM AUTHOR]

Purpose : We investigated the in vitro effects of human mast cell chymase on corneal epithelial cells. Methods : Human corneal epithelial cells were incubated with human chymase at activity levels that were likely to exist in the tears of patients with vernal keratoconjunctivitis. Results : Incubation of chymase resulted in a decrease of barrier function of corneal epithelium. Occludin protein was cleaved by chymase. In the wound assay, incubation with chymase resulted in an inhibition of cell migration. Conclusion : Human chymase causes the proteolysis of occludin and fibronectin, resulting in a decrease of barrier function and inhibition of the migration of corneal epithelial cells. [ABSTRACT FROM AUTHOR]

Corneal transplantation is one of the most successful forms of solid organ transplantation; however, immune rejection is still a major cause of corneal graft failure. Both innate and adaptive immunity play a significant role in allograft tolerance. Therefore, immune cells, cytokines, and signal-transduction pathways are critical therapeutic targets. In this analysis, we aimed to review the current literature on various immunotherapeutic approaches for corneal-allograft rejection using the PubMed, EMBASE, Web of Science, Cochrane, and China National Knowledge Infrastructure. Retrievable data for meta-analysis were screened and assessed. The review, which evaluated multiple immunotherapeutic approaches to prevent corneal allograft rejection, showed extensive involvement of innate and adaptive immunity components. Understanding the contribution of this immune diversity to the ocular surface is critical for ensuring corneal allograft survival. [ABSTRACT FROM AUTHOR]