Stromal Graft Rejection Research Articles

Approaches toward enhancing survival probability following deep anterior lamellar keratoplasty.

The greatest advantage of deep anterior lamellar keratoplasty over full-thickness corneal transplantation is the elimination of graft failure caused by endothelial rejection. Despite this advantage, a deep anterior lamellar keratoplasty graft can fail because of several factors, such as complications related to the donor–recipient interface, graft epithelial abnormalities, graft vascularization, stromal graft rejection, and recurrence of herpetic keratitis. Increased deep anterior lamellar keratoplasty graft survival is mainly built upon optimization of the ocular surface to provide a hospitable environment for the graft. Any predisposing factors for graft epithelial abnormalities, corneal neovascularization, and preexisting vernal keratoconjunctivitis should be identified and treated preoperatively. Prompt recognition and appropriate treatment of interface-related complications and stromal graft rejection usually result in good anatomic outcomes, with no detrimental effects on vision.

Deep anterior lamellar keratoplasty combined with antiviral therapy in the treatment of severe herpes necrotizing stromal keratitis

Objective: To evaluate the efficacy of modified deep lamellar keratoplasty (DLKP) combined with antiviral medications for severe herpes necrotizing stromal keratitis. Methods: Retrospective case series study. Modified DLKP was performed in combination with antiviral medications in fifty patients (50 eyes) with severe necrotizing stromal keratitis, which was unresponsive to systemic and topical antiviral treatment for 1 week, at Shandong Eye Hospital. Before surgery, the operated eyes were examined using slit-lamp microscopy. The size of corneal ulceration and inflammatory infiltration and the depth of ulceration were observed in all of the patients. Corneal scraping and microbial culture and confocal laser scanning microscopy were used to exclude fungal, bacterial, Acanthamoeba, or other infections, and check the number of corneal endothelial cells. Anterior segment optical coherence tomography was used to examine the depth of infiltration, especially the thickness of the remaining cornea below the deepest ulceration. Antiviral drugs were used topically and systemically to control the infection and inflammation. Postoperatively, both antiviral drugs and low-dose corticosteroids were used. The ocular inflammation, corneal graft status and viral recurrence were monitored intraoperatively and postoperatively. Results: All of the fifty patients showed obvious inflammatory infiltration and stromal ulcers, and the corneal stroma in 23 patients (46%) remained less than 1/5 of the corneal thickness. Nine (18%) of the patients presented with descemetocele. The depth of infiltration ranged from 128 μm to 519 μm [mean, (265±84) μm]. The depth of corneal ulcers was deeper than 2/3 of the corneal thickness in 36 eyes (72%). The endothelial cells were visible in 26 eyes. The density of endothelial cells ranged from 1 275 cells/mm(2) to 2 994 cells/mm(2) [mean, (2 053±507) cells/mm(2)]. No fungal or bacterial infection was detected by corneal scraping. The microbial culture results were negative. All the inflammations in patients with severe herpes necrotizing stromal keratitis were under control by DLKP. No intraoperative corneal perforation occurred, and 6 eyes (12%) healed following amniotic membrane transplantation due to slow corneal epithelial healing. The infection was exacerbated two days following the surgery in two eyes (4%). These infections were controlled with enhanced antiviral medications in addition to the immediate withdrawal of corticosteroids. The corneal grafts returned to transparency at 1-2 weeks in 42 eyes (84%). Ten eyes (20%) exhibited recurrence due to medication withdrawal without the doctors' advice and a lack of regular visit during 2-year follow-up. Two patients (4%) developed stromal graft rejection for the same reasons. Conclusions: DLKP can achieve the results of ulcer healing for severe herpes necrotizing stromal keratitis. Combined antiviral therapy and close follow-up can reduce the viral recurrence. (Chin J Ophthalmol, 2018, 54: 97-104).

Big bubble deep anterior lamellar keratoplasty for management of deep fungal keratitis.

Objective. To evaluate the therapeutic effect of big bubble deep anterior lamellar keratoplasty (DALK) in patients with deep fungal keratitis. Methods.Consecutive patients who had DALK for deep fungal keratitis at Shandong Eye Hospital between July 2011 and December 2012 were included. In all patients, the infiltration depth was more than 4/5ths of the corneal thickness. DALK surgery was performed with bare Descemet membrane (DM) using the big bubble technique. Corrected distance visual acuity (CDVA), graft status, and intraoperative and postoperative complications were monitored. Results. Big bubble DALK was performed in 23 patients (23 eyes). Intraoperative perforation of the DM occurred in two eyes (8.7%) during stromal dissection. The patients received lamellar keratoplasty with an air bubble injected into the anterior chamber. Double anterior chamber formed in 3 eyes (13.0%). Mean CDVA of the patients without cataract, amblyopia, and fungal recurrence was improved from preoperative HM/20 cm−1.0 (LogMAR) to 0.23 ± 0.13 (LogMAR) at the last followup (P < 0.01). Fungal recurrence was found in two patients (8.7%). Corneal stromal graft rejection was noted in one patient (4.3%). Conclusions. DALK using the big bubble technique seems to be effective and safe in the treatment of deep fungal keratitis unresponsive to medication.

Deep Anterior Lamellar Keratoplasty for the Treatment of Stromal Corneal Dystrophies

To report the perioperative complications and clinical outcomes after deep anterior lamellar keratoplasty (DALK) using the big bubble technique in eyes with stromal corneal dystrophies. Seventy-four eyes of 65 patients who underwent DALK for stromal corneal dystrophies were evaluated in this retrospective interventional case series study. Main outcome measures were intraoperative and postoperative complications, postoperative uncorrected visual acuity, best spectacle-corrected visual acuity, spherical equivalent refraction, and topographic astigmatism. There were 44 eyes with macular corneal dystrophy, 18 eyes with lattice dystrophy, and 12 eyes with granular dystrophy. DALK was completed in 69 cases (94.6%). Descemet membrane microperforations occurred in 6 eyes (8.7%). The mean follow-up period was 43.5 ± 23.9 months, ranging from 12 to 96 months. Postoperative best spectacle-corrected visual acuity of 0.5 or better was present in 52 of 69 eyes (75.4%). There were 3 episodes of stromal graft rejection, which responded to topical therapy. Lattice dystrophy recurred in 6 eyes (35.3%). DALK using the big bubble technique is an effective procedure in the treatment of patients with corneal stromal dystrophies. Recurrence of lattice dystrophy was relatively high.

Corneal Allograft Rejection: Immunopathogenesis to Therapeutics

Corneal transplantation is among the most successful solid organ transplants. However, despite low rejection rates of grafts in the ‘low-risk’ setting, rejection can be as high as 70% when grafted into ‘high-risk’ recipient beds. Under normal homeostatic conditions, the avascular cornea provides a unique environment that facilitates immune and angiogenic privilege. An imbalance in pro-inflammatory, angiogenic and lymphangiogenic mediators leads to a breakdown in corneal immune privilege with a consequent host response against the donor graft. Recent developments in lamellar and endothelial keratoplasties have reduced the rates of graft rejection even more, while providing improved visual outcomes. The corneal layer against which an immune response is initiated, largely determines reversibility of the acute episode. While epithelial and stromal graft rejection may be treated with topical corticosteroids with higher success, acute endothelial rejection mandates a more aggressive approach to therapy due to the lack of regenerative capacity of this layer. However, current immunosuppressive regimens come with the caveat of ocular and systemic side effects, making prolonged aggressive treatment undesirable. With the advent of biologics, efficacious therapies with a superior side effect profile are on the horizon. In our review we discuss the mediators of ocular immune privilege, the roles of cellular and molecular immune players in graft rejection, with a focus on human leukocyte antigen and antigen presenting cells. Furthermore, we discuss the clinical risk factors for graft rejection and compare rates of rejection in lamellar and endothelial keratoplasties to traditional penetrating keratoplasty. Lastly, we present the current and upcoming measures of therapeutic strategies to manage and treat graft rejection, including an overview of biologics and small molecule therapy.

Long‐term results of deep anterior lamellar keratoplasty in patients with keratoconus

AbstractPurpose Long‐term endothelial cell density changes and visual and refractive outcomes after descemetic (d) and predescemetic (pd) deep anterior lamellar keratoplasty (DALK) using the big‐bubble technique in eyes with keratoconus.Methods Retrospective, consecutive, non‐comparative, case series analysis of 95 eyes that have undergone DALK for keratoconus using the big‐bubble technique with at least 1 year of follow‐up. Big‐bubble was achieved in 74 (77.9%) eyes (dDALK), whereas 21 (22.1%) eyes underwent manual lamellar dissection (pdDALK) because of failed big‐bubble.Results Descemet ruptures occurred in 13 of 95 cases (13.7%). Five ruptures (5.3%) were converted to penetrating keratoplasty. Mean length of follow‐up was 5.3 years (range, 1‐8 years). Postoperative best spectacle‐corrected visual acuity was significantly better in dDALK group than in pdDALK group at years 1 and 2. But, at the final examinations, there was no significant difference between the study groups (0.25 ± 0.22 logarithm of the minimum angle of resolution in dDALK group and 0.33 ± 0.15 logarithm of the minimum angle of resolution in pdDALK group; p = 0.12). The 2 groups were comparable regarding astigmatism and spherical equivalent refractive error throughout the follow‐up period. Mean endothelial cell loss was 22.5 ± 17.9% at last follow‐up with most of the loss occurring in the first year (8.7% ± 5.6%). Stromal graft rejection episodes occurred in 3 eyes (3.2%), which resolved with appropriate therapy.Conclusion DALK using the big‐bubble technique is effective in patients with keratoconus. In DALK, manual lamellar dissection is a reasonable alternative when big‐bubble separation of the Descemet membrane is not achieved.

Big-bubble deep anterior lamellar keratoplasty for post-keratitis and post-traumatic corneal stromal scars

Evaluation of outcomes of big-bubble deep anterior lamellar keratoplasty in cases with post-keratitis and post-traumatic corneal scars. Interventional case series. Patients with corneal stromal scarring secondary to healed infectious keratitis or trauma were recruited from the Corneal Clinic of the M. M. Joshi Eye Institute, Karnataka, India between August 2007 and December 2009. All patients underwent big-bubble deep anterior lamellar keratoplasty surgery. Best-corrected visual acuity, as well as intra- and postoperative complications. Big-bubble deep anterior lamellar keratoplasty was performed in 36 patients (25 males, 11 females) with post-infectious keratitis (n = 22) and post-traumatic (n = 14) corneal stromal scars sparing the Descemet's membrane and endothelium. Mean age was 39.7 ± 11.3 years (range: 22-58 years). Although a big bubble was achieved in all eyes (100%), intraoperative perforation of the Descemet's membrane occurred in six eyes (16%) during stromal dissection. Two cases required conversion to penetrating keratoplasty. A double anterior chamber occurred in the immediate postoperative period in three cases (8.3%). Raised intraocular pressure was seen in one eye. Mean preoperative best-corrected visual acuity (0.03 ± 0.04) improved significantly at the end of 6 months follow-up postoperatively (0.43 ± 0.20; P < 0.01, Wilcoxon signed-ranks test). Corneal stromal graft rejection was noted in two cases (5.5%) during the first 3 months after surgery. Graft failure occurred in two cases (5.5%). Deep anterior lamellar keratoplasty using the big-bubble technique is a viable option in cases with post-infectious keratitis and post-traumatic corneal stromal scarring with normal Descemet's membrane and endothelium.

Deep Anterior Lamellar Keratoplasty Using Big-Bubble Technique for Treatment of Corneal Stromal Scars

To report the clinical outcomes of deep anterior lamellar keratoplasty (DALK) in patients with anterior corneal stromal scars associated with various etiologies. A total of 79 eyes of 79 patients with corneal stromal scars sparing the Descemet membrane and the endothelium underwent DALK by using big-bubble technique. The main outcome measures of the study were the ability to successfully complete DALK, intraoperative and postoperative complications, best spectacle-corrected visual acuity, refraction, and graft clarity. Seventy-two of the surgical procedures were carried out as DALK, and the mean follow-up time was 28.1 ± 17.9 months (range, 12-78 months). The most frequent indication for DALK surgery was postherpetic keratitis (44%). Complete Descemet membrane exposure via big bubble (descemetic DALK) could be achieved in 57 cases (79%). Fifteen eyes (21%) required layer-by-layer manual dissection (predescemetic DALK). Best spectacle-corrected visual acuity of 6/12 or better was present in 59 eyes (82%) postoperatively. The mean spherical equivalent and topographic astigmatism were -3.32 ± 2.13 (range, -9.13 to +4.75) and -2.97 ± 1.94 (range, -8.0 to +4.50) diopter, respectively. There were 2 instances of stromal graft rejection, which responded to medical therapy. DALK big-bubble technique may be a valuable and safe treatment in patients with corneal stromal scar with healthy endothelium. The visual and refractive outcomes are comparable to standard penetrating keratoplasty, avoiding the risk of endothelial rejection.

Long-Term Results of Deep Anterior Lamellar Keratoplasty for the Treatment of Keratoconus

To evaluate the long-term endothelial cell density (ECD) changes and visual and refractive outcomes after deep anterior lamellar keratoplasty (DALK) using the big-bubble technique in eyes with keratoconus. Retrospective interventional case series study. setting: Single hospital. patients: Two hundred forty-one eyes of 214 patients who underwent DALK for moderate to advanced keratoconus. main outcome measures: Intraoperative and postoperative complications, postoperative uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), spherical equivalent refraction, topographic astigmatism, and ECD. Two hundred thirty-four procedures (97%) were completed as DALK. Big bubble was successfully achieved in 193 eyes (82.4%). In 7 eyes (3%), the procedure was converted to penetrating keratoplasty because of Descemet membrane macroperforations. Microperforations occurred in 18 eyes (7.5%). The mean follow-up time was 50.5 ± 22.2 months (range 24 to 96 months). UCVA was lower than 20/100 in all eyes preoperatively and better than 20/100 in 191 eyes (81.6%) postoperatively. BSCVA was 20/40 or better in 187 eyes (79.9%) and 20/20 or better in 38 eyes (16.2%). The mean (± SD) preoperative ECD that was possible in 166 eyes was 2797 ± 561 cells/mm(2). Mean (± SD) endothelial cell loss was 8.1% ± 4.6% at 1 year, 10.5% ± 5.7% at 2 years, 15.1% ± 14.8% at 6 years, and 22.5% ± 15.9% at 8 years. Stromal graft rejection episodes occurred in 4 eyes, which resolved with appropriate therapy. Deep anterior lamellar keratoplasty that uses the big-bubble technique is effective in patients with keratoconus. Long-term endothelial cell loss was moderate and lower than penetrating keratoplasty grafts.

Presumed Corneal Stromal Graft Rejection After Deep Anterior Lamellar Keratoplasty in a Patient with Systemic Lupus Erythematosis

To report a case of presumed corneal stromal graft rejection after deep anterior lamellar keratoplasty in a patient with systemic lupus erythematosis (SLE). Deep anterior lamellar keratoplasty was performed using the "bug bubble" technique in the left eye of a 14-year-old patient with keratoconus. Her medical records revealed a history of SLE that was in remission. Immediate postoperative course was uneventful. A best-corrected visual acuity (BCVA) of 20/40 was achieved at the end of 6 months. She was advised to taper off and stop topical corticosteroids by the end of 9 months. The patient presented with a red eye and reduced vision 11 months after surgery. At the time of presentation, the BCVA was 20/200, and ultrasonic central corneal thickness (CCT) was 792 μm in the operated eye. The anterior chamber was found to be quiet, and posterior segment examination was unremarkable. A diagnosis of presumed immune-mediated corneal stromal graft rejection was made. Treatment was started in the form of 1% prednisolone acetate eye drops every hour and 0.5% moxifloxacin hydrochloride eye drops thrice times daily. Hundred milligrams of methylprednisolone in 150 mL of 20% dextrose was administered intravenously. At the end of 2 weeks, the corneal edema cleared with a resultant CCT of 618 μm, and the BCVA improved to 20/40. Deep anterior lamellar keratoplasty does not eliminate the risk of corneal stromal rejection. Our patient had an associated history of SLE, which may necessitate a prolonged topical immunosuppression after corneal transplantation in these cases.

Efficacy and Safety of Moxifloxacin as an Additive in Optisol-GS a Preservation Medium for Corneal Donor Tissue

To assess the endothelial toxicity and the microbiological efficacy of moxifloxacin (250 microg/mL) as an additive to Optisol-GS. Five hundred nine donor rims were studied. One half of each donor rim was placed in standard Optisol-GS and the other half of the rim in Optisol-GS fortified with moxifloxacin (250 microg/mL). All rims were refrigerated for 24 hours at 3 degrees C and placed in thioglycolate broth and incubated at 37 degrees C for 7 days. One pair of donor buttons not used in transplantation stored in each solution was examined for endothelial changes by using electron microscopy (EM). A second pair of cornea buttons was examined for toxicity by endothelial staining with 0.3% trypan blue and 0.2% alizarin red. All endothelial cells that stained (nonviable cells) and nonstained cells (viable cells) were counted, and the ratio of nonviable cells was calculated. The rate of culture-positive donor rims in the Optisol-GS group was 11.9% (61/509) and in the moxifloxacin-fortified Optisol-GS media was 2.5% (13/509). The difference was statistically significant (P < 0.01; chi test). There was no difference in the cellular morphology of the button stored in moxifloxacin-fortified Optisol-GS compared with Optisol-GS using EM. In the bioassay, the rate of nonviable cells in the moxifloxacin-fortified media compared with the control media was nonsignificant (P > 0.05). Moxifloxacin (250 microg/mL) seems to be safe as an additive agent for cornea storage media. It significantly reduces the rate of positive rim cultures and shows no signs of endothelial cytotoxicity as viewed by EM and by a bioassay of trypan blue and alizarin red.

Mooren's Ulcer and Evidence of Stromal Graft Rejection After Penetrating Keratoplasty

A Mooren's ulcer developed in a 6-year-old girl after a penetrating keratoplasty for Peters' anomaly. A destructive, circumferential, and centripetal stromal ulceration recurred despite conjunctival resection, corneal gluing, topical and systemic administration of corticosteroids, and repeat graftings. Results of a systemic and a rheumatologic examination were unremarkable. Histopathologic evaluations of donor grafts consistently disclosed a lymphocytic and a plasma cell infiltrate. Indirect immunofluorescent staining using a normal donor cornea substrate was positive at the level of Bowman's membrane and stroma. The patient's lymphocytes were stimulated by a partially purified bovine corneal antigen and a positive antibody titer was found in the patient's sera to the same corneal antigen. These results suggest humoral and cell-mediated immune mechanisms can be involved in the initiation and perpetuation of a stromal rejection process after penetrating keratoplasty.