[Factors Affecting Outcomes of Repeated Penetrating Keratoplasty].

PURPOSE: To investigate prognosis for repeated penetrating keratoplasty (PKP) and factors that affect the outcome. METHODS: We retrospectively investigated graft survival rates, 1-year postoperative best-corrected visual acuity and irreversible rejection rates in 108 eyes of 106 patients that had repeated PKP. Factors that might affect the outcome were, age, number of previous PKP, original diseases, history of glaucoma and rejection and the use of postoperative immunosuppressant were also studied. RESULTS: Individual-factor analysis showed that history of rejection and postoperative immunosuppressant significantly increased the risk of postoperative rejection. Multi-factor analysis showed that graft survival rate was significantly lower among cases that had systemic immunosuppressants (steroids and cyclosporine). One year postoperative best-corrected visual acuity was significantly worse in cases that had history of glaucoma. In cases with history of rejection, systemic administration of postoperative immunosuppressants was significantly associated with postoperative irreversible rejection. CONCLUSION: History of rejection and glaucoma tend to have poor outcome, and the outcome might not improve by postoperative immunosuppressants.

Prognostic factors for corneal graft recovery after severe corneal graft rejection following penetrating keratoplasty.

BACKGROUND: To investigate the outcome and prognostic factors for corneal graft recovery after severe corneal graft rejection following penetrating keratoplasty (PKP) treated with topical and systemic steroids. METHODS: Fifty-eight eyes in 58 patients with severe corneal graft rejection following PKP were treated with topical and systemic steroids. Factors affecting the reversibility and maintenance of graft transparency were analyzed. RESULTS: Graft transparency was restored in 37 of 58 eyes (63.8%). Clarity of the graft was maintained in 25 of 37 eyes after transparency was restored, while corneal decompensation developed at a mean of 6.0 ± 4.3 months in the remainder. The interval between rejection and treatment with systemic steroids was shorter in cases that recovered graft transparency (OR, 0.88, 95% CI. 0.80-0.97, P = 0.0093). Corneal decompensation after the recovery of corneal transparency tend to occur in cases of regraft (OR, 0.09, 95% CI. 0.01-0.54, P = 0.0091). CONCLUSIONS: Severe corneal graft rejection after PKP was reversible in approximately two-thirds of the cases, with graft transparency being maintained in two-thirds of them when treated with both topical and systemic steroids. Early treatment confers a benefit in terms of the recovery of graft transparency.

Morphological evaluation of meibomian glands using noncontact infrared meibography.

Meibography is used to study morphological changes in the meibomian glands (MGs), and semiquantitative analysis has been used for MG assessment. We conducted a detailed morphometric assessment of MGs using noncontact infrared meibography (NIM) and investigated the relationship between MG morphology and the ocular surface and MG morphology associated with aging and sex in 37 subjects. The MGs in the upper and lower eyelids showed significant correlations in their morphology, with the former having longer ducts than the latter. The mean length of the MG ducts, percent area of MG acini, and number of gland dropouts were significantly correlated with age. The mean length of the MG ducts in the upper and lower eyelids showed negative correlations with the meibum (P=.043) and fluorescein staining score (P=.008), respectively. The percent area of MG acini in the upper eyelid showed a positive correlation with tear film breakup time (P=.012) and negative correlations with tear film lipid layer interferometry and meibum (P=.005 and .002, respectively). The mean length of the male's MG ducts in the lower eyelid was significantly longer than that of the females (P=.03). These results indicate that morphometric analysis using NIM may be useful for assessing ocular surface conditions.

Efficacy and safety of long-term corticosteroid eye drops after penetrating keratoplasty: a prospective, randomized, clinical trial.

PURPOSE: Endothelial rejection remains a major cause of graft failure after penetrating keratoplasty (PKP). Topical corticosteroids are the gold standard for preventing rejection; however, protocols for corticosteroid treatment have been diverse. The aim of the present study was to examine the efficacy and safety of long-term use of corticosteroid eye drops after PKP in a randomized, clinical trial. DESIGN: Randomized, nonblinded, clinical trial. PARTICIPANTS: We enrolled 42 patients (21 males and 21 females) with a mean age of 65.3 years who underwent PKP and maintained graft clarity for >1 year with topical steroid eye drops. INTERVENTION: Patients were randomly assigned to 1 of 2 groups: Administration of 0.1% fluorometholone 3 times a day (steroid group) or discontinuation of steroid eye drops (no steroid group). All patients were followed for 12 months. MAIN OUTCOME MEASURES: Proportion of eyes without endothelial rejection and the proportion of eyes with clear grafts and the incidence of local or systemic side effects. RESULTS: Of the initial 42 patients, 4 in the steroid group and 6 in the no steroid group did not complete the trial. Of the patients who completed the trial, 1 patient in the steroid group and 6 in the no steroid group developed endothelial rejection at an average of 5.2±4.5 (mean ± standard deviation) months after study enrollment. The difference in the incidence of rejection between groups was found to be significant by both chi-square (P = 0.027) and Kaplan-Meier analyses (log-rank test, P = 0.032). No difference was observed between the 2 groups in visual acuity, intraocular pressure, epithelial damage, tear-film break-up time, cataract progression, infection, or incidence of systemic side effects. CONCLUSIONS: Prolonged use of 0.1% fluorometholone was beneficial for the prevention of rejection after PKP. Because no adverse consequences were noted, we recommend continuing use of the low-dose corticosteroids, even in non-high-risk cases.

Aetiology-specific comparison of long-term outcome of deep anterior lamellar keratoplasty for corneal diseases.

AIMS: To evaluate the long-term outcome of deep anterior lamellar keratoplasty (DALK) for the treatment of herpetic keratitis, keratoconus, stromal scars and corneal dystrophies. METHODS: This retrospective consecutive case study includes 275 consecutive eyes of 254 patients who underwent DALK; 35 eyes with herpetic keratitis, 114 eyes with stromal scar, 93 eyes with keratoconus and 67 eyes with corneal dystrophy. Exclusion criteria included therapeutic DALK for the treatment of descemetocele or infectious keratitis, and eyes with limbal stem cell deficiency. Patients were examined at 1, 3 and 6 months, and 1, 3 and 5 years after DALK. Graft survival rate, best corrected visual acuity (BCVA), endothelial cell density (ECD) and postoperative complications were evaluated. RESULTS: The mean postoperative follow-up duration was 51±41 months. The graft survival rate of all subjects was 96.8% at 1 year, 89.9% at 3 years, 83.5% at 5 years and 74.1% at 10 years. At 6 months, BCVA significantly improved from 1.14±0.54 to 0.22±0.21 in the keratoconus group, from 1.13±0.60 to 0.44±0.54 in the herpes group, from 1.00±0.59 to 0.49±0.38 in the stromal scar group and from 1.04±0.52 to 0.32±0.29 in the corneal dystrophy group (all, p<0.0001). BCVA stabilised after 6 months thereafter up to 5 years. ECD decreased just after DALK and maintained >1000 cell/mm(2) at 5 years in all groups. CONCLUSIONS: DALK provides good visual acuity with slight ECD decrease over long term in all groups.

How Much Progress Has Been Made in Corneal Transplantation?

To assess the benefits of component lamellar corneal surgery, we investigated the surgical outcomes of deep anterior lamellar keratoplasty (DALK) for keratoconus and Descemet stripping automated endothelial keratoplasty (DSAEK) for laser iridotomy-induced bullous keratopathy (LI-BK). The results were compared with the surgical outcomes of penetrating keratoplasty (PKP). Seventy-nine eyes with keratoconus treated with DALK and 81 eyes with LI-BK treated with DSAEK were studied, and the graft clarity rate, best spectacle-corrected visual acuity, endothelial cell density (ECD), and surgical complications were compared with 273 eyes with keratoconus and 98 eyes with LI-BK all treated with PKP. Keratoconus eyes showed excellent visual outcomes with DALK and PKP, but graft survival was higher for PKP (100%, 98.9%, and 96.3% vs. 98.6%, 90.6%, and 86.1%, at 1, 3, and 5 years after surgery, respectively; P < 0.0001). There were no significant differences in the ECD up to 1 year after surgery. Greater ECD decline was observed for PKP at 3 and 5 years after surgery. Descemet membrane microperforation was observed in 49 eyes treated with DALK. Postoperative complications in eyes treated with PKP were increased incidence of immunological rejection and secondary glaucoma compared with eyes treated with DALK. LI-BK graft survival rates were excellent in both groups (DSAEK: 89.6% and 86.1%; PKP: 100% and 98.6%, 1- and 2-year rates, respectively; P = 0.17). Best spectacle-corrected visual acuity was better in the DSAEK group, and ECD showed a higher rate of decrease with DSAEK than with PKP. DALK and DSAEK considerably improved surgical outcomes in eyes with keratoconus and those with LI-BK, respectively. However, several key areas require further work, including development of safe surgical methods in DALK and prevention of early postoperative ECD loss in DSAEK.

Effects of corneal irregular astigmatism on visual acuity after conventional and femtosecond laser-assisted Descemet's stripping automated endothelial keratoplasty.

PURPOSE: To compare short-term outcomes of Descemet's stripping automated endothelial keratoplasty (DSAEK) using a graft prepared with either a femtosecond laser or a microkeratome. METHODS: Thirty-eight patients underwent DSAEK with grafts prepared with either a femtosecond laser (f-DSAEK; 21 eyes) or a microkeratome (m-DSAEK; 17 eyes). Visual acuity, endothelial cell density, regular astigmatism and irregular astigmatism were compared between the two groups preoperatively and at 1, 3, and 6 months post-operatively. Fourier analysis was conducted to calculate astigmatism of the anterior and posterior surfaces, and total cornea, using anterior segment optical coherence tomography (AS-OCT). RESULTS: Visual acuity (logMAR) improved from 1.20 ± 0.60 to 0.43 ± 0.25 after m-DSAEK (P < 0.001) and from 1.20 ± 0.57 to 0.77 ± 0.33 after f-DSAEK (P = 0.0028) at 6 months following DSAEK. Visual acuity after m-DSAEK was significantly better than after f-DSAEK at 1, 3, and 6 months (P < 0.05). AS-OCT corneal images revealed greater irregularities on the posterior surfaces of f-DSAEK grafts compared to m-DSAEK grafts. Irregular astigmatism of the total cornea and the posterior surface was significantly larger after f-DSAEK than after m-DSAEK, although there was no significant difference in irregular astigmatism of the anterior surface at 6 months. Postoperative visual acuity was significantly correlated with the postoperative irregular astigmatism of the total cornea (r = 0.6657 and P < 0.001) and the anterior (r = 0.416, P = 0.016) and posterior surfaces (r = 0.7046, P < 0.001). CONCLUSIONS: Visual outcomes after f-DSAEK were poor compared to conventional m-DSAEK due to an increase in irregular astigmatism caused by posterior surface irregularities.

Ocular surface reconstruction by cultivated epithelial sheet transplantation.

Recent advances in ocular surface reconstruction for patients with severe ocular surface diseases have significantly improved the prognosis of patients with vision-impairing corneal abnormalities. The history of cultivated epithelial sheet transplantation is short, and debate on the current approaches for these procedures is continuing. Limbal stem cell transplantation, including conjunctivolimbal autograft and keratolimbal allograft, has brought opportunities for vision improvement. In addition, the use of cultivated limbal epithelial transplantation from both allogeneic and autologous sources has provided further options for immediate postoperative epithelialization of the corneal surface. Finally, cultivated oral mucosal epithelial transplantation, which allows autologous transplantation for patients with bilateral limbal stem cell deficiency, has provided the best overall midterm and long-term results. Its biggest advantages are the absence of rejection reactions and the reduction of postoperative complications associated with steroid therapy. However, a solitary surgical approach is not sufficient for obtaining a good clinical outcome. To maximize the possibility of success using these procedures, it is important to preoperatively enhance aggressive treatment of the ocular surface, especially with factors that facilitate moisture retention. In this review article, we also discuss our clinical experience in relation to these surgical procedures.

Symptoms, visual function, and mucin expression of eyes with tear film instability.

PURPOSE: We examined symptoms, tear stability, visual function, and conjunctival cytology in eyes with an unstable tear film (UTF), expressed as a short tear film breakup time without epithelial damage or low tear secretion, and compared the results with those from eyes with aqueous deficiency (AD) associated with epithelial damage, and healthy eyes. METHODS: We divided the patients with ocular discomfort into 2 groups according to the breakup time, Schirmer value, and epithelial staining score: UTF group (≤5 seconds, >5 mm, and <3 points; 21 eyes of 21 patients) and AD group (≤5 seconds, ≤5 mm, and ≥3 points; 21 eyes of 21 patients). We examined all patients and 17 healthy subjects for symptoms, tear functions, tear film stability by tear film lipid layer interferometry and tear film analysis system, and functional visual acuity. Conjunctival impression cytology was performed to investigate changes in goblet cell density, squamous metaplasia, and messenger RNA expression of MUC5AC and MUC16. RESULTS: The symptom scores, tear film analysis system index, and functional visual acuity testing were significantly worse in the UTF and AD groups compared with those in the control group (P < 0.05). The messenger RNA expression levels of MUC5AC and MUC16 were significantly lower in UTF and AD eyes compared with those in the control eyes (P < 0.0001). CONCLUSIONS: An UTF itself can cause dry eye symptoms and visual disturbance comparable with those of AD dry eyes.

Effects of diquafosol sodium eye drops on tear film stability in short BUT type of dry eye.

PURPOSE: To investigate the effects of diquafosol sodium (DQS) eye drops, a purinergic P2Y2 receptor agonist, on tear film stability in patients with unstable tear film (UTF). METHODS: Two prospective studies were conducted. One was an exploratory nonrandomized trial on 39 eyes with dry eye symptoms and short tear film break-up time (BUT), but without epithelial damage. Changes in symptoms, BUT, Schirmer value, and ocular surface fluorescein staining (FS) scores were studied for 3 months. The other was a randomized clinical trial of DQS and artificial tears (AT) in 17 eyes with short BUT. Eyes with decreased Schirmer values (≤ 5 mm) were excluded. Changes in symptoms, BUT, FS scores, and tear film stability using continuous corneal topographic analysis were studied for 4 weeks. RESULTS: In the exploratory study, while Schirmer values were not significantly increased, significant improvements in symptoms and BUT were noted at both 1 and 3 months. In the randomized clinical trial, significant improvements in symptoms were noted in the DQS group, but not in the AT group, at 2 weeks. BUT was significantly prolonged in the DQS group at 4 weeks but not in the AT group. No significant changes were noted in FS scores or tear film stability. CONCLUSIONS: DQS improved subjective symptoms and prolonged BUT in eyes with UTF not associated with low tear secretion and ocular surface epithelial damage. Because many patients who have UTF are refractory to conventional treatments, DQS may offer benefits in the treatment of dry eyes.

Changes in corneal sensation, epithelial damage, and tear function after descemet stripping automated endothelial keratoplasty.

PURPOSE: To study the ocular surface changes in eyes after Descemet stripping automated endothelial keratoplasty (DSAEK) compared with those after penetrating keratoplasty (PKP). METHODS: This prospective study compared the changes in 31 eyes of 28 patients who underwent DSAEK (DSAEK group) with those in 15 disease-matched eyes of 15 patients who underwent PKP (PKP group). Corneal epithelial integrity was evaluated using a fluorescein staining score. Corneal sensation was measured with a Cochet-Bonnet esthesiometer. Tear function was evaluated using the Schirmer test, tear clearance test, tear function index, and tear break-up time. RESULTS: The postoperative fluorescein staining score was significantly higher in the PKP group than in the DSAEK group (P = 0.02). Postoperative corneal sensation was significantly better in the DSAEK group than in the PKP group (P < 0.01). Corneal sensation after DSAEK was significantly better than the preoperative value (P = 0.02). There were no statistically significant changes in the Schirmer test, tear clearance test, tear function index, or break-up time before and after the surgery in both the DSAEK and PKP groups. No significant differences were observed between the DSAEK and PKP groups after the surgery. CONCLUSIONS: Corneal sensation was preserved, and epithelial damage was less severe after DSAEK compared with PKP. Preservation of corneal sensation may contribute to the early recovery of visual function and long-term maintenance of ocular surface health after DSAEK.

Descemet stripping automated endothelial keratoplasty for bullous keratopathy with an irregular posterior surface.

PURPOSE: To investigate the efficacy and safety of Descemet stripping automated endothelial keratoplasty (DSAEK) for bullous keratopathy with an irregular posterior surface of the cornea caused by anterior-posterior radial keratotomy or forceps injury. The results were compared with eyes that had undergone penetrating keratoplasty (PKP). METHODS: Six eyes of 6 Japanese patients (mean age, 52.0 years) who underwent DSAEK between 2007 and 2012 were analyzed retrospectively. Of the 6 cases, 5 were birth injuries and 1 resulted from anterior-posterior keratotomy. Five of the 6 cases had mild-to-moderate amblyopia. The clinical results of DSAEK were compared with the outcomes of disease-matched cases treated with PKP [19 eyes of 18 patients (mean age, 58.4 years): 9 cases were birth injuries and 10 resulted from anterior-posterior keratotomy]. Subjective symptoms, graft clarity, best-corrected visual acuity, corneal astigmatism, postoperative endothelial cell density, posterior irregularity, and intraoperative and postoperative complications were evaluated. RESULTS: All grafts were attached successfully without double chamber formation following DSAEK. The corneas remained clear throughout the observation period, and the subjective symptoms improved in all cases. Significant improvement was observed in the best spectacle-corrected visual acuity and posterior irregularity in all the patients. No significant difference in corneal astigmatism was observed between the DSAEK and PKP groups. The mean endothelial cell density was 1450 cells per square millimeter 6 months postoperatively in the DSAEK group, which was similar to that in the PKP group. CONCLUSIONS: DSAEK is considered to be useful, even in bullous keratopathy eyes with an irregular posterior surface.

Keratoplasty postoperative treatment update.

Immunosuppressive therapy is the main postoperative treatment for keratoplasty, but there are considerable differences in protocols for the use of steroids and other immunosuppressants. Therefore, we conducted 2 prospective randomized clinical trials and 1 prospective nonrandomized clinical trial on keratoplasty postoperative treatment. One study evaluated the efficacy and safety of long-term topical corticosteroids after a penetrating keratoplasty was performed. Patients who underwent keratoplasty and maintained graft clarity for >1 year were randomly assigned to either a steroid or a no-steroid group. At the 12-month follow-up, the no-steroid group developed significantly more endothelial rejection than did the steroid group. A second study elucidated the effectiveness and safety of systemic cyclosporine in high-risk corneal transplantation. The patients were assigned to a systemic cyclosporine or control group. At a mean follow-up of 42.7 months, no difference was observed in the endothelial rejection rates and graft clarity loss between the 2 groups. A third study elucidated the effectiveness and the safety of systemic tacrolimus in high-risk corneal transplantation. Of 11 consecutive eyes decompensated despite systemic cyclosporine treatment, there was no irreversible rejection in eyes treated with tacrolimus, which was significantly better than in previous penetrating keratoplasty with systemic cyclosporine treatment. Prognosis after keratoplasty in patients with keratoconus is relatively good, but special attention is required for patients with atopic dermatitis. Postkeratoplasty atopic sclerokeratitis (PKAS) is a severe form of sclerokeratitis after keratoplasty in atopic patients. Our retrospective study showed that 35 eyes of 29 patients from a total of 247 keratoconus eyes undergoing keratoplasty were associated with atopic dermatitis, of which 6 eyes of 5 patients developed PKAS. Eyes with PKAS had a significantly higher incidence of atopic blepharitis and preoperative corneal neovascularization, and therefore, we suggest systemic corticosteroids or cyclosporine to prevent PKAS in such high-risk cases.

Surgically induced necrotizing scleritis after primary pterygium surgery with conjunctival autograft.

BACKGROUND: Although pterygium excision with conjunctival autograft is a widely performed surgical procedure, surgically induced necrotizing scleritis (SINS) following such surgery is extremely rare. METHODS: A 68-year-old man underwent nasal pterygium excision with conjunctival autograft uneventfully. On postoperative day 17, the conjunctival graft was avascular, with epithelial defect. Although topical steroid and antibacterial treatments were continued, the graft and sclera melted, with the ischemic sclera showing gradual thinning. The thinning area spread to the adjoining cornea, and active inflammation with epithelial defect was observed adjacent to the site of thinning. RESULTS: Systemic and microbiological examination was noncontributory. The patient was suspected of having SINS, and administration of oral prednisolone was started. Although the necrotic area was reduced temporarily, medication was discontinued due to nausea, and the area of thinning increased. Conjunctival flap surgery was later performed, and the graft was well accepted. CONCLUSIONS: SINS must be considered in the differential diagnosis of patients with scleritis following pterygium surgery, especially if radiation or mitomycin C has not been used.