A Detailed Analysis of Individuals Having Graft Failure After Corneal Transplantation.

PURPOSE: To describe demographic and clinical characteristics of patients with graft failure after keratoplasty, determine the cause of graft failure and outcomes. METHODS: The charts of patients between 2008-2013 in the Cornea Service at Wills Eye Hospital with a history of a corneal transplant before the end of 2012 were retrospectively reviewed. Included were patients who had graft failure after corneal transplantation and had at least one year of follow-up after transplantation. Penetrating keratoplasty (PK) and Descemet's stripping endothelial keratoplasty (DSEK) patients were analyzed separately. RESULTS: A total of 186 eyes of 170 patients with graft failure after a PK (156) or DSEK (30) procedures were identified. The baseline characteristics included 100 female and 70 male patients with an age between 0 and 90 years (median 63 years). At the time of surgery, 38% had three or more systemic diseases and 68% were using three or more systemic medicines. Mean follow up time for PK was nearly four times of DSEK. Only 2 DSEK eyes (7%) underwent a 3rd DSEK graft, while 47 (30%) PK eyes underwent a 3rd PK and 15 (10%) PK eyes underwent more than three PK procedures. CONCLUSIONS: Most DSEK failures occurred in 1st year, while graft failure in PKs is scattered over years. Failure in DSEK is mostly due to graft or surgical risk factors but in PK mostly due to factors in the host. DSEK does not appear to be as affected by the patients' demographic and clinical characteristics as much as PK.

Glutathione S-transferase expression in benign and malignant eyelid tumors.

Eyelid tumors commonly originate from the skin and its appendages. Environmental toxins and oxidants affect eyelid carcinogenesis. Glutathione S-transferases (GST) are antioxidants that participate in pathogenesis. We investigated GST levels in malignant and benign eyelid tumors in otherwise healthy individuals. We used 57 malignant eyelid biopsies, benign eyelid biopsies, and tissue removed during blepharoplasty and entropion operations culled from pathology archives. Specimens were divided into three groups: malignant lesions, benign lesions and controls consisting of eyelid tissue removed during routine blepharoplasty and entropion surgery. Specimens were immunostained for seven GST (GST-A, GST-P, GST-Z, GST-S, GST-K, GST-O, GST-T) and the intensity of staining was quantified. In the malignant group, GST-O and GST-P staining was less intense than for the control group. In the benign group, the GST-P level was less than for the control group. We found no significant difference between the intensity of staining in malignant and benign groups. Our findings suggest that GST-O and GST-P enzymes may play significant roles in eyelid carcinogenesis.

Small-angle hypertropia in a case of inferior rectus aplasia: an intraoperative surprise.

Introduction: The clinical features of congenital inferior rectus (IR) aplasia are similar to IR paresis/palsy, and they include hypertropia, limitation of downgaze - especially in abduction, incyclotorsion, A-pattern strabismus, and abnormal head posture.Case report: A 22-year-old man presented with a right face turn, small-angle hypertropia (14 prism diopters) in the right eye, and limitation of downgaze that passed the midline; no diplopia was present and supraduction was normal in that eye. Double Maddox rod revealed 12 degrees of incyclotorsion for the right eye. The Titmus test revealed a stereo acuity of 400 seconds of arc. Based on the preoperative clinical findings, a presumptive diagnosis of IR paresis was made and a surgical plan for performing superior rectus muscle recession and IR muscle resection was devised. Intraoperatively, forced duction test was positive in depression. To our surprise, after performing a 4 mm recession of the superior rectus muscle, we found that the IR muscle was absent. We then revised the surgical plan and performed a 6 mm resection and anterior transposition of the inferior oblique (IO) muscle. Post-operatively, the patient was orthophoric in the primary position without diplopia, and his abnormal head posture was significantly improved.Conclusion: The amount of primary position hypertropia and severity of downgaze limitation are not adequate for differentiating congenital IR aplasia from IR paresis/palsy. Orbital imaging including CT, MRI or anterior segment optical coherence tomography (AS-OCT, UBM) is helpful to distinguish these two entities preoperatively.

Topical 0.03% tacrolimus versus systemic mycophenolate mofetil as adjuncts to systemic corticosteroids for preventing graft rejection after repeat keratoplasty: one-year results of a randomized clinical trial.

PURPOSE: To compare the efficacy of topical 0.03% tacrolimus in combination with systemic corticosteroids versus systemic mycophenolate mofetil (MMF) and corticosteroids in preventing corneal allograft rejection after repeat keratoplasty. METHODS: This prospective, randomized clinical trial enrolled 63 consecutive eyes of 63 patients who underwent repeat keratoplasty after a failed penetrating keratoplasty. Group 1 (32 eyes) received MMF orally 1 g twice daily for the first 6 months and then 1 g daily for the next 6 months, and group 2 (31 eyes) received topical 0.03% tacrolimus four times a day for 12 months. All patients were treated with topical and oral corticosteroids postoperatively. The participants were observed closely for signs of graft rejection, and the rates of rejection-free graft survival were calculated and compared between the two groups at postoperative month 12. RESULTS: The groups were balanced in patient's age and risk factors for graft rejection (e.g., original diagnosis, number of previous grafts, and quadrants of corneal vascularization). Endothelial graft rejection occurred in 5 eyes (15.6%) of group 1 and 6 eyes (19.4%) of group 2 (P = 0.75). Irreversible endothelial graft rejection resulting in graft failure occurred in 3 eyes of each group (P = 0.99). The rate of rejection-free graft survival was 84.4% in group 1 and 80.6% in group 2 at postoperative month 12 (P = 0.74). CONCLUSION: Topical 0.03% tacrolimus was as effective as systemic MMF as adjuncts to topical and systemic corticosteroids in reducing endothelial graft rejection with 12 months follow up after repeat keratoplasty.

Conjunctivitis: A Systematic Review.

Conjunctivitis is a commonly encountered condition in ophthalmology clinics throughout the world. In the management of suspected cases of conjunctivitis, alarming signs for more serious intraocular conditions, such as severe pain, decreased vision, and painful pupillary reaction, must be considered. Additionally, a thorough medical and ophthalmic history should be obtained and a thorough physical examination should be done in patients with atypical findings and chronic course. Concurrent physical exam findings with relevant history may reveal the presence of a systemic condition with involvement of the conjunctiva. Viral conjunctivitis remains to be the most common overall cause of conjunctivitis. Bacterial conjunctivitis is encountered less frequently and it is the second most common cause of infectious conjunctivitis. Allergic conjunctivitis is encountered in nearly half of the population and the findings include itching, mucoid discharge, chemosis, and eyelid edema. Long-term usage of eye drops with preservatives in a patient with conjunctival irritation and discharge points to the toxic conjunctivitis as the underlying etiology. Effective management of conjunctivitis includes timely diagnosis, appropriate differentiation of the various etiologies, and appropriate treatment.

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.

Appropriate stage of Descemet membrane removal during donor preparation in deep anterior lamellar keratoplasty.

PURPOSE: To investigate the appropriate surgical stage for Descemet membrane (DM) removal during donor preparation in deep anterior lamellar keratoplasty (DALK). METHODS: This study included 83 corneoscleral buttons that were used for DALK. The donor DM was removed randomly either before (group 1; 43 eyes) or after (group 2; 40 eyes) trephination. The time required for DM removal was recorded, and the geometric properties of cut buttons were evaluated after trephination. The intraoperative video recordings were reviewed to determine if the dissections were performed at the stroma-DM plane as it was intended. The time needed to remove the DM, the rate of correct dissection at the intended stroma-DM plane, and the roundness and precision of the donor cuts were compared between the groups. RESULTS: The two groups were comparable in donor characteristics, including age, quality of the tissue, and trephination size. Time spent to remove DM was significantly shorter in group 1 (68.9 ± 48.2 s) than group 2 (117.7 ± 52.7 s, P = 0.001). DM stripping was performed incorrectly in 2 corneas (4.7%) in group 1 and in 12 corneas (30%) in group 2 (P = 0.01). No difference was found between the groups in the roundness and precision of donor button cuts. CONCLUSIONS: DM removal before trephination did not detrimentally affect the geometric properties of punched donor tissues. When DM stripping was performed before trephination, the donor tissue was less traumatized and posterior graft surface was more likely to be regular; therefore, it is advisable to remove DM before trephination during donor preparation for DALK.

Characterization of In Vivo Biomechanical Properties in Macular Corneal Dystrophy.

PURPOSE: To measure and compare corneal biomechanics in patients with macular corneal dystrophy (MCD), versus those who underwent penetrating keratoplasty (PK) for MCD, versus normal subjects. DESIGN: Cross-sectional study. METHODS: This study enrolled 24 eyes with MCD, 25 eyes that underwent PK in patients with preoperative diagnosis of MCD, and 28 normal eyes. The ocular response analyzer was used to measure corneal biomechanical properties, including corneal resistance factor (CRF) and corneal hysteresis (CH). Intraocular pressure (IOP) was measured using a Goldmann applanation tonometer, and central corneal thickness (CCT) was measured using an ultrasonic pachymeter. The CCT, CRF, CH, and IOP were compared among the study group. RESULTS: CCT was significantly lower in the MCD group (423 ± 47 mµ) than in the PK group (541 ± 31 mµ; P < .001) and the controls (540 ± 26 mµ; P < .001). Meanwhile, CCT was comparable between the PK and control groups (P = .98). CRF did not differ between the MCD (8.34 ± 2.12 mm Hg) and the PK (8.66 ± 1.66 mm Hg) groups (P = .89); however, both of these groups had lower CRF values than the control (9.76 ± 1.83 mm Hg, P = .02) group. No significant differences were observed among the 3 groups in CH (P = .13). IOP values did not differ between the MCD (11.25 ± 1.69 mm Hg) and PK (12.0 ± 2.67 mm Hg) groups (P = .95); however, the IOP values for both of these groups differed significantly from those of the controls (13.46 ± 2.17 mm Hg; P = .006). CONCLUSIONS: CRF was significantly reduced in MCD and did not return to normal values even after PK. The reduced corneal rigidity could result in underestimating IOP in patients with MCD and in those undergoing PK for this stromal dystrophy.

Peripheral Hypertrophic Subepithelial Opacities of Corneal Grafts After Deep Anterior Lamellar Keratoplasty.

PURPOSE: To investigate possible underlying etiologies of the development of peripheral graft hypertrophic subepithelial opacities (PGHSO) and to evaluate the effects of these opacities on visual outcomes after deep anterior lamellar keratoplasty (DALK). METHODS: This prospective, interventional case series enrolled 29 eyes with keratoconus that underwent DALK and developed PGHSO (group 1). The control group consisted of 32 eyes with keratoconus that underwent DALK during the same period and had a clear graft at the final examination (group 2). Possible underlying risk factors for the development of PGHSO were investigated, and postoperative refractive and topographic outcomes were compared between the 2 study groups. RESULTS: Eyes of group 1 had well-defined elevated peripheral subepithelial opacities of the corneal graft, originating from the donor-recipient junction. The central 4-mm area of the graft was clear in all eyes of this group. Compared with the controls, group 1 had flatter grafts at postoperative month 1 and a longer time interval from surgery to initial suture removal. The 2 study groups were comparable in other investigated factors, including the severity of keratoconus, surgical technique, duration of topical steroid use, and donor quality. No significant differences were observed between the case and control groups in postoperative visual acuity and graft surface regularity. CONCLUSIONS: Graft flattening during the early postoperative period and prolonged time interval from surgery to initial suture removal might be factors predisposing to the development of PGHSO. This complication did not affect postoperative visual outcomes when the central 4-mm area of the graft remained clear.

Configuration of recipient corneal cut after mechanical trephination in keratoconus.

PURPOSE: To determine the roundness of recipient corneal cuts after mechanical trephination and to investigate possible factors that could affect the corneal bed configuration in deep anterior lamellar keratoplasty (DALK). METHODS: This study enrolled 85 eyes with keratoconus that underwent DALK. Recipient corneas were partially trephined using a new, unused, disposable Hessburg-Barron suction trephine. Photographs that best represented the recipient corneal cut were selected, and ImageJ software was used to evaluate the roundness of recipient bed. The effect of potential variables on the roundness of cuts was investigated using the univariate analyses. RESULTS: The mean patient age was 31.0 ± 9.0 years. The mean recipient trephine size was 8.04 ± 0.29 mm (range 7.5-8.50 mm). The recipient cut roundness was 0.922 ± 0.070, varying from 0.78 to 1.0. The roundness of the corneoscleral limbus (0.874 ± 0.074) which represented the shape of recipient cornea was the main predictor of the configuration of recipient cut (r = 0.84, P < 0.001). Other preoperative characteristics investigated were mean keratometry (P = 0.63), keratometric astigmatism (P = 0.18), central corneal thickness (P = 0.64), keratoconus severity (P = 0.37), and trephine size (P = 0.50) that demonstrated no significant associations with the roundness of cut. CONCLUSIONS: The recipient corneal cut after mechanical trephination may not be circular. The roundness of recipient bed was primarily affected by the roundness of corneoscleral limbus, indicating that the shape of recipient cut tends to follow the original shape of the cornea.

Goldmann Applanation Tonometer Versus Ocular Response Analyzer for Measuring Intraocular Pressure After Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: To evaluate agreement between IOP measured using the ocular response analyzer (ORA) versus using the Goldmann applanation tonometer (GAT) in patients treated by Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: This prospective, case-control study comprised 38 normal eyes and 37 post-DSAEK eyes. IOP was measured using the GAT (IOPGAT). The ORA was used to measure corneal biomechanics and cornea-compensated IOP (IOPCC). Corneal hysteresis (CH), corneal resistance factor, and IOP measurements of the 2 groups were compared. Intertonometer agreement was evaluated in each study group using Bland-Altman plots and 95% limits of agreement. Univariate analysis was used to evaluate the effect of independent factors on the difference between the 2 IOP readings (ΔIOP). RESULTS: The IOPCC and IOPGAT readings showed no significant intergroup differences. IOPCC was significantly higher than IOPGAT, with a mean difference of 3.0 ± 3.3 mm Hg in the normal group (P < 0.001) and 4.5 ± 3.1 mm Hg in the DSAEK group (P < 0.001). The 95% limits of agreement for the IOPCC and IOPGAT was between -3.4 and 9.5 mm Hg and between -1.6 and 10.6 mm Hg in the normal and DSAEK groups, respectively. CH (r = -0.57, P < 0.001) and donor thickness (r = 0.81, P = 0.04) were identified as the main predictors of ΔIOP after DSAEK. ΔIOP did not vary significantly with the central corneal thickness or corneal resistance factor. CONCLUSIONS: The IOPGAT and IOPCC were significantly different, which indicates that the GAT and ORA cannot be used interchangeably for measuring IOP after DSAEK. The difference between these 2 measurements was primarily affected by the variations in CH and donor thickness.

Therapeutic approaches for corneal neovascularization.

Angiogenesis refers to new blood vessels that originate from pre-existing vascular structures. Corneal neovascularization which can lead to compromised visual acuity occurs in a wide variety of corneal pathologies. A large subset of measures has been advocated to prevent and/or treat corneal neovascularization with varying degrees of success. These approaches include topical corticosteroid administration, laser treatment, cautery, and fine needle diathermy. Since the imbalance between proangiogenic agents and antiangiogenic agents primarily mediate the process of corneal neovascularization, recent therapies are intended to disrupt the different steps in the synthesis and actions of proangiogenic factors. These approaches, however, are only partially effective and may lead to several side effects. The aim of this article is to review the most relevant treatments for corneal neovascularization available so far.

Safety and efficacy of autologous serum eye drop for treatment of dry eyes in graft-versus-host disease.

PURPOSE: To evaluate the treatment of autologous serum eye drops (ASED) on dry eyes in patients with graft-versus-host disease (GVHD). METHODS: A retrospective chart review of 35 patients with a history of ocular GVHD following hematopoietic stem cell transplantation that used ASED to alleviate dry eye symptoms was performed. Patients were categorized into three different groups. If patients had available ophthalmic data before and after starting treatment was group 1 (n = 14), had available ophthalmic data after starting treatment in group 2 (n = 10) and had available ophthalmic data before treatment or did not have any data after starting treatment in group 3 (n = 11). Data were collected on patient's age, gender, primary diagnosis, visual acuity and fluorescein corneal staining were collected on individual eyes in order to evaluate the efficacy of the ASED on alleviating dry eye-related signs and symptoms. RESULTS: No adverse ocular effect from the ASED was found in our series (except one fungal keratitis). All patients reported either improvement (55%) or stability (45%) in their ocular symptoms upon the use of ASED. In patients with available data before and after starting treatment, the corneal staining score improved by a median of 1 (p = 0.003) and the LogMAR visual acuity had a non-significant improvement. CONCLUSION: In our study, ASED used by patients with ocular GVHD were both safe and effective. ASED should be considered in patients with GVHD who suffer from dry eyes.

Is There an Increased Prevalence of Asteroid Hyalosis in Eyes with Uveal Melanoma? A Histopathologic Study.

During the planning meeting for the Collaborative Ocular Melanoma Study (COMS) prior to the start of patient recruitment in 1986, there was an interest expressed in determining whether a relationship existed between the presence of uveal melanoma (UM) and asteroid hyalosis (AH). To answer this question, the ophthalmic examination form (unlike the pathology form for enucleated eyes) for each COMS patient asked whether AH was present or not. Though an increased prevalence was not found, this result was never published. A recent unpublished study at the University of Wisconsin School of Veterinary Medicine indicated a higher prevalence of AH in canine eyes with UM when compared to control eyes (without tumor) enucleated for goniodysgenesis. This further increased our interest in revisiting the published literature, clinical records, and histopathology slides of the enucleated eyes from the COMS study, as well as the histopathology slides on file in the University of Wisconsin Eye Pathology Laboratory. While cases with both AH and UM were occasionally encountered in the literature, clinically, we could not find a previous study focusing on these two processes. This study was conducted to explore whether such an association exists.

Survival of Primary Penetrating Keratoplasty in Children.

PURPOSE: To review the indications and outcomes of children undergoing primary penetrating keratoplasty and identify prognostic factors for graft survival. DESIGN: Retrospective, interventional case series. METHODS: Medical records of every child 12 years of age or younger who underwent primary penetrating keratoplasty at Wills Eye Hospital Cornea Service between 2007 and 2015 were reviewed. Survival of the primary graft was analyzed using the Kaplan-Meier survival method. RESULTS: Forty-six eyes of 35 children underwent primary keratoplasty during the study period. The mean age at the time of primary keratoplasty was 24.6 ± 39.9 months. The mean follow-up duration was 36.4 ± 28.8 months. Congenital opacity was the most common diagnosis for primary keratoplasty (89.1%). The overall mean graft survival time was 45.2 ± 5.8 months, with a survival rate of 75.7% at 1 year. The 1-year graft survival rate was 51.9% and 90.7% in eyes with and without glaucoma, respectively. Cox proportional hazards regression analysis demonstrated that the presence of glaucoma (P = .014) and concurrent operation during primary keratoplasty (P = .049) were independent prognostic factors for poor graft survival. On the other hand, age of primary keratoplasty (P = .626) and operation before or after primary keratoplasty (P = .800 and P = .104, respectively) were not associated with poorer graft survival. Half of our patients were able to achieve ambulatory vision at the last follow-up. CONCLUSION: Although pediatric penetrating keratoplasty is challenging, successful transplantation with good graft survival can be obtained. Better understanding of prognostic factors can possibly improve graft survival in the future.

Influence of Early Descemet Stripping Endothelial Keratoplasty on Visual Outcomes in Pseudophakic Corneal Edema.

PURPOSE: Longstanding corneal edema can lead to anterior stromal scarring that may limit visual acuity following Descemet stripping endothelial keratoplasty (DSEK). The ideal time to perform DSEK to prevent permanent changes is unclear. Our aim is to determine whether earlier DSEK is associated with improved visual outcomes. DESIGN: Cohort study. METHODS: Setting: Institutional. STUDY POPULATION: Total of 120 eyes of patients who underwent DSEK for corneal edema following cataract surgery (CE); 87% of eyes had a diagnosis of Fuchs dystrophy. INTERVENTION: Post-DSEK visual acuity was compared in patients who underwent DSEK ≤6 months vs >6 months after CE. Linear and logistic regression were performed to assess the relationships between DSEK timing and best spectacle-corrected visual acuity (BSCVA) while accounting for baseline preoperative patient characteristics. MAIN OUTCOME MEASURES: Postoperative best-corrected visual acuity 6 months after DSEK (POM6 BSCVA). RESULTS: Median CE-to-DSEK time was 8.62 (interquartile range [IQR] 12.28) months (n = 120). Overall median preoperative VA and POM6 BSCVA were 0.54 (IQR 0.68) and 0.24 (IQR 0.16), respectively. Median POM6 BSCVA was better in patients with CE-to-DSEK time ≤6 months (median 0.18, IQR 0.19) vs >6 months (median 0.30, IQR 0.21) (P = .014). A significant relationship was found between CE-to-DSEK time and POM6 BSCVA (coefficient = 0.002, P = .033), accounting for preoperative vision and pachymetry. Patients who underwent DSEK ≤6 months after CE were more likely to achieve POM6 BSCVA better than 20/40 (odds ratio = 3.73 P = .035). CONCLUSION: Performing earlier DSEK for pseudophakic corneal edema appears to be associated with improved vision. Further prospective study is warranted to determine the optimal time to perform DSEK in patients with pseudophakic corneal edema.

Trocar-Assisted, Sutureless, Scleral-Fixated Intraocular Lens Implantation Combined With Penetrating Keratoplasty.

PURPOSE: To evaluate the results of trocar-assisted, sutureless, scleral-fixated (SSF) intraocular lens (IOL) implantation combined with penetrating keratoplasty (PKP). METHODS: This study comprised 4 eyes (4 patients) undergoing trocar-assisted SSF-IOL implantation during PKP. The combined technique was performed in 3 eyes of 3 patients with bullous keratopathy and in 1 eye with central corneal opacity. Two eyes had anterior chamber IOL implants, and 2 were aphakic. All eyes had inadequate capsular support. Evaluated parameters were biomicroscopy, corrected distance visual acuity, intraocular pressure, IOL position, and corneal graft status. Intraoperative and postoperative complications and additional surgeries were recorded. RESULTS: The mean follow-up period was 28.3 ± 3.5 months. Trocar-assisted SSF-IOL implantation with PKP was successfully performed in all eyes. Visual acuity improved in all patients. During the follow-up period, a well-stabilized IOL without any IOL-related complication was obtained in all eyes. In one eye with corneal scarring and aphakic glaucoma caused by trauma, drug-resistant glaucoma developed 6 months after surgery requiring Express glaucoma shunt surgery. In one eye with a history of central retinal vein occlusion, repeat keratoplasty was performed after 10 months because of graft rejection. CONCLUSIONS: Trocar-assisted SSF-IOL implantation combined with PKP is an alternative method for visual rehabilitation in the eyes with bullous keratopathy and corneal scarring without sufficient capsular support.