1044
ARTICLE
Clinical course and outcomes in patients with Mooren ulcer who had cataract surgery Shilpa Das, MS, Ashik Mohamed, MTech, Virender S. Sangwan, MS
Purpose: To report outcomes of cataract surgery in patients with Mooren ulcer.
Setting: L.V. Prasad Eye Institute, Hyderabad, India. Design: Retrospective case series. Methods: The medical records of patients with Mooren ulcer who had cataract surgery between 2000 and 2015 were assessed. The main outcome measures were the role of preoperative immunosuppression and disease inactivity, cataract surgery safety, visual outcomes, and postoperative ulcer recurrence. Results: Of 22 patients (26 eyes), the mean corneal ulceration was 6.8 clock hours G 2.9 (SD). Corticosteroids were the most commonly used (84.6% of the 26 eyes) preoperative immunosuppression agents and 38.5% of the 26 eyes were under maintenance immunosuppression. The median disease inactivity before surgery was 7 months. Cataract surgery was extracapsular in 10 patients, small incision in 3 patients, and phacoemulsification in 13 patients.
M
ooren ulcer, a noninfectious idiopathic peripheral ulcerative keratitis, is an autoimmune disorder characterized by painful ulceration of the peripheral cornea. Since its initial description by Albert Mooren in 1867,1 several clinicians have studied its pathogenesis and manifestations, and highlighted various treatment modalities. The disease has a chronic course characterized by exacerbations and remissions.2 The main modality of management is local and systemic immunosuppression.3 In addition, surgical modalities, such as conjunctival resection, tissue adhesives, patch grafts, and lamellar and penetrating keratoplasty (PKP), have been advocated for management of this disease.4 Sequelae secondary to the keratitis, such as corneal scarring, irregular corneal contour, iridocorneal synechiae, secondary glaucoma, and complicated
Twenty-two eyes had scleral incisions. The median follow-up was 6 months (interquartile range, 10 months). The median corrected distance visual acuity (CDVA) improved from 1.48 logarithm of minimum angle of resolution (logMAR) before surgery to 0.30 and 0.35 logMAR at 1 month and at the last follow-up after surgery, respectively (P % .0001). Mooren ulcer recurred in 5 eyes between 3 months and 7 years after surgery. No disease activity was seen in the immediate postoperative period. No significant risk factors for disease recurrence were noted.
Conclusions: With adequate immunosuppression, cataract surgery in eyes with Mooren ulcer was safe and CDVA improved significantly with no disease reactivation immediately after surgery. No proven role of maintenance immunosuppression was observed. The type of cataract surgery had no influence on ulcer reactivation. Patients with a disease-free interval of 6 months or more before surgery and those who had scleral incisions had favorable outcomes. J Cataract Refract Surg 2017; 43:1044–1049 Q 2017 ASCRS and ESCRS
cataract, can cause significant visual impairment even if the active disease resolves. Cataract surgery for complicated or senile cataract in these patients is a decision that often needs to be made in the clinic. It has been proposed that surgical trauma such as that from keratoplasty or cataract surgery itself, if performed during the active phase of the disease, can cause reactivation or worsening of ulceration.5,6 In addition, studies have shown that previous corneal trauma or surgery might have a role in the pathogenesis of Mooren ulcer in a previously uninvolved eye by exposure of concealed corneal antigens to antigen-presenting cells, resulting in intense infiltration of lymphocytes.7,8 Hence, important aspects to watch for are the timing of cataract surgery as well as the occurrence or recurrence or worsening of ulceration after cataract surgery.
Submitted: December 9, 2016 | Final revision submitted: May 7, 2017 | Accepted: May 21, 2017 From the Prof. Brien Holden Eye Research Centre (Das), Ophthalmic Biophysics (Mohamed), and the Cornea, Ocular Immunology and Uveitis Service, L.V. Prasad Eye Institute, Hyderabad, Telangana, India. Corresponding author: Virender S. Sangwan, MS (Ophthalmology), Cornea, Ocular Immunology and Uveitis Service, L.V. Prasad Eye Institute, L.V. Prasad Marg, Road No.2, Banjara hills, Hyderabad-500034, Telangana, India. E-mail: [email protected]. Q 2017 ASCRS and ESCRS Published by Elsevier Inc.
0886-3350/$ - see frontmatter http://dx.doi.org/10.1016/j.jcrs.2017.05.034
1045
CATARACT SURGERY OUTCOMES IN MOOREN ULCER PATIENTS
From earlier reports of outcomes of cataract surgery in patients with Mooren ulcer, much of what is known has been gleaned from isolated case reports and small case series.5,9,10 We previously reported outcomes of cataract surgery in 6 eyes with Mooren ulcer from our center.11 In the current study, we assessed a much larger cohort of this relatively rare group of patients to evaluate the effect of immunosuppression, disease inactivity, and type of cataract surgery on the postoperative outcomes.
Table 1. Distribution of eyes with Mooren ulcer by peripheral corneal involvement. Involvement %3 clock hours O3–6 clock hours O6–9 clock hours O9–12 clock hours
Eyes (n) 3 12 6 5
documented at 3, 6, 12, 18, and 24 months and at each patient’s last visit after cataract surgery.
PATIENTS AND METHODS Study Design and Patients In this retrospective study, the medical records of all patients diagnosed with Mooren ulcer who had cataract surgery between January 2000 and August 2015 at L.V. Prasad Eye Institute, Hyderabad, India, were reviewed. Institutional Review Board approval was obtained (LEC number 12-15-129). The diagnosis of Mooren ulcer was based on the characteristic clinical features of crescentshaped peripheral corneal ulcer with overhanging margins, cellular infiltration at the advancing edge, circumferential spread, no scleral involvement, and absence of associated systemic disease.4 The research methods adhered to the tenets of the Declaration of Helsinki. Preoperative Data Assessment The clinical information analyzed included preoperative data such as visual acuity, pattern of ulceration, type and duration of immunosuppressive therapy, surgical management for active ulceration, and period of disease inactivity. To describe ulcer location and extent, the peripheral cornea was divided into 4 quadrants and 12 clock hours. The superior quadrant spanned from clock hours 10:30 to 1:30, the inferior from 4:30 to 7:30, the nasal from 1:30 to 4:30, and the temporal from 7:30 to 10:30. (For nasal and temporal quadrants, clock hours were exchanged depending on the eye involved.) Bilateral cases were treated as independent data. Based on clinical presentation, tailored therapy with topical and systemic immunosuppression was given to patients in accordance with the severity-based stepladder approach.12 This depended on ulcer laterality, corneal quadrants involved, stromal loss, and presence of perforation. The various drugs used for immunosuppression included topical, oral or intravenous steroids (prednisolone or methyl prednisolone), and oral or intravenous immunosuppressants (folic acid analogs, antimetabolites, or alkylating agents). Surgical treatment included conjunctival resection, tissue adhesives, and corneal patch grafts, when indicated. Intraoperative Data Assessment The indication for cataract surgery in these patients was significant visual impairment because of cataract, assessed by slitlamp examination. Surgery was performed after complete resolution of active disease, and surgery type as well as site was individualized based on the grade of cataract and area of peripheral corneal involvement. The area of previous ulceration or thinning was avoided as much as possible. Site, incision, and type of cataract surgery performed were documented. Postoperative Data Assessment Postoperatively, all patients received prednisolone acetate 1.0% eyedrops for a minimum of 6 weeks in weekly tapering doses, starting with a frequency of 6 times per day with antibiotic drops 4 times a day for 1 week. The postoperative follow-up included at least a minimum of 3 evaluations (1 day, 1 week, and 5 weeks) for each patient (except 1 patient who was lost to follow-up after 1 week). Thereafter, visual acuity and signs of ulcer recurrence were
Statistical Analysis Statistical analysis was performed using the statistical software Origin (version 7.0, Origin Lab Corp.). Continuous data were checked for normality using the Shapiro-Wilk test and were described using mean and standard deviation (parametric data) or median and interquartile range (IQR) (nonparametric data). The variances between 2 datasets were checked for equality using the Levene test. The independent t test (independent samples) and paired t test (nonindependent samples) were used to compare parametric data with equal variance. The Mann-Whitney test (independent samples) and Wilcoxon signed-rank test (nonindependent samples) were used to compare parametric data with unequal variance and nonparametric data. The Fisher exact test was used to compare the categorical data. A P value of 0.05 or less was considered statistically significant.
RESULTS Patient Demographics and Disease Pattern
A total of 281 patients diagnosed with Mooren ulcer were seen between 2000 and 2015, of whom 22 patients (26 eyes) had cataract surgery; the cataract surgery rate was 7.8%. In the cohort of 22 patients, the median age at presentation was 62.5 years (IQR, 25) and male-to-female ratio was 17:5. Five patients (22.7%) had unilateral Mooren ulcer and 17 patients (77.3%) had bilateral ulceration, of whom 4 patients had cataract surgery in both eyes. A mean of 6.8 clock hours G 2.9 (SD) (range 2 to 12 clock hours) of peripheral corneal ulceration was seen at presentation. Table 1 shows the distribution of Mooren ulcer in various clock hours of the peripheral cornea. The inferior quadrant of the peripheral cornea was most commonly involved (23 eyes, 89%) followed by nasal (20 eyes, 77%). Treatment
Twenty-two eyes received medical treatment and 20 eyes received both medical and surgical treatment to control ulcer activity before the cataract surgery. In 4 cases, the disease was inactive at presentation. Corticosteroids (topical and/or systemic) were the most commonly used (n Z 22 [84.6%]) for pre-cataract surgery immunosuppression. The combination of topical and oral steroids was the most used immunosuppression treatment of choice (31% [n Z 8]). The median duration of immunosuppression before cataract surgery was 6.8 months (IQR, 15.5). Figure 1 shows the distribution of preoperative immunosuppression therapy. Table 2 shows the surgical treatment the patients received before cataract surgery. The median period of disease inactivity before cataract surgery was Volume 43 Issue 8 August 2017
1046
CATARACT SURGERY OUTCOMES IN MOOREN ULCER PATIENTS
Figure 1. Preoperative immunosuppression distribution in patients with Mooren ulcer (IV Z intravenous).
7 months (IQR, 22), and 16 cases (61.5%) had a quiescent period of 6 months or more. Just before cataract surgery, 10 (38.5%) of the 26 eyes were under maintenance immunosuppression (10 topical; 4 topical and systemic), given selectively to control active disease. Cataract Surgery and Postoperative Course
Patients had different varieties of cataract surgery, incision type, and surgical site distribution. Areas of previous ulceration/thinning were avoided as much as possible. In 8 of 26 eyes, placement of the surgical incision close to an area of previous ulceration was unavoidable because of the nearly total extent of peripheral involvement. Ten patients (38.5%) had extracapsular cataract extraction (ECCE), 3 patients (11.5%) had small-incision cataract surgery (SICS), and 13 patients (50.0%) had phacoemulsification surgery. Twenty-two eyes (84.6%) had a scleral incision. The median follow-up after surgery was 6 months (IQR, 20). Patients received immunosuppression treatment after cataract surgery for a median of 6 weeks (IQR, 3), with a total range of 1 week to 12.4 years. In addition to the 6-week regimen of topical prednisolone acetate 1.0% eyedrops given to all patients, 4 patients received oral steroids (prednisolone 1 mg/kg a day, gradually tapered) and 1 patient received additional oral immunosuppressants (azathioprine 100 mg a day in divided doses) because of a greater severity of the initial ulceration. Visual Acuity
The mean corrected distance visual acuity (CDVA) at presentation was 0.78 G 0.55 logarithm of the minimum angle of resolution (logMAR) (range 0.00 to 2.09 logMAR). The median CDVA significantly improved after cataract
Table 2. Treatment before cataract surgery. Treatment 1. None 2. Conjunctival resection plus tissue adhesive 3. Patch graft 4. Both (2) and (3)
Volume 43 Issue 8 August 2017
Eyes, n (%) 6 (23.1) 16 (61.5) 3 (11.5) 1 (3.9)
surgery at 1 month and at the last follow-up (both P Z .0001). Figure 2 compares the CDVA preoperatively and postoperatively. The CDVA improved in all patients after cataract surgery except 2, the first patient had graft failure after PKP that was performed after cataract surgery and the second had central corneal scarring. Figure 3 shows postoperative outcomes in 3 patients. Ulcer Reactivation
Active ulceration recurred in 5 eyes (19.2%) between 3 months and 7 years after cataract surgery; they were appropriately managed. Figure 4 shows Mooren ulcer reactivation in a patient after cataract surgery. No recurrences were seen in the immediate postoperative period. Table 3 shows the characteristics of the recurrence cases. No statistically significant association was found between the possible risk factors and recurrence of active ulceration after cataract surgery (Table 4). DISCUSSION Mooren ulcer is a persistent peripheral ulcerative keratitis with a chronic course and repeated bouts of inflammation.3 It has varied manifestations with respect to age, sex, laterality, and severity of condition. The demographics vary in different parts of the world. In the southern part of India, studies have shown male preponderance with an average age of presentation between 50 and 65 years.8,12–14 The sex and age distribution in our patients were similar. Considerable evidence supports the notion that Mooren ulcer is an autoimmune disorder.15 Patients with this disease have infiltrating leucocytes in corneal specimens, as well as circulating immune complexes to stromal antigens.16,17 Immunosuppression is the main modality of treatment of Mooren ulcer.18 The various drugs used for immunosuppression in our patients included topical, oral or intravenous steroids (prednisolone or methyl prednisolone), and oral or intravenous immunosuppressives (folic acid analogs, antimetabolites, or alkylating agents). Based on our experience, the immunosuppression regimen in this study followed a stepladder approach as per ulcer severity. This depended on ulcer laterality, corneal
CATARACT SURGERY OUTCOMES IN MOOREN ULCER PATIENTS
Figure 2. Significant improvement in CDVA after cataract surgery at 1 month (Month1) and at each patient’s last visit (Final) compared with before cataract surgery (Pre) CDVA (CDVA Z corrected distance visual acuity; IQR Z interquartile range; logMAR Z logarithm of the minimum angle of resolution).
quadrants involved, stromal loss, and the presence of perforation (described previously by our group12). The most common treatment received by our patients was a combination of oral steroids and topical steroids (approximately one third of patients). With adequate immunosuppression, all ulcers healed. For any autoimmune disease with multiple exacerbations despite primary treatment, the principle of immunosuppressive regimen is to keep patients on a minimum dose maintenance therapy that will suppress the disease process. Indiscriminate use of immunosuppressives can cause unwanted side effects. To our knowledge, no studies to date have analyzed the role of maintenance immunosuppressive therapy in preventing recurrent inflammation in Mooren ulcer cases. The role of such therapy becomes more crucial to ascertain if cataract surgery is being planned in these patients given the evidence that surgery itself can trigger inflammation.7,8 Furthermore, some surgeons might believe that administering additional prophylactic immunosuppressives before surgery in anticipation of inflammation might be useful. Of the studies of cataract surgery in patients with Mooren ulcer thus far, 1 case report described the use of low-dose immunosuppression (oral cyclophosphamide)
1047
until cataract surgery and the addition of immunosuppressives (oral steroids) 1 day before surgery.5 In our study, 10 of 26 cases were on selective low-dose maintenance immunosuppression before cataract surgery (6 eyes on topical; 4 eyes on topical and systemic) and no additional immunosuppressives were introduced before surgery. Of the 5 patients who had ulcer recurrence in our study, 4 belonged to this category (P Z 0.055, univariate analysis assessing correlation). This might suggest that the disease severity was greater in these patients and the recurrence of active ulceration was inevitable. Alternatively, one might propose that maintenance immunosuppressive therapy provided no benefit toward preventing ulcer reactivation. We might hypothesize that although immunosuppressives are required (primary and maintenance) to keep the disease quiescent, there is no proof that maintenance or additive immunosuppressive therapy before cataract surgery plays a role in the prevention of ulcer reactivation. However, further studies are needed to validate this hypothesis. In general, the eye of any patient should be quiet before cataract surgery is performed. In 2 studies of phacoemulsification surgery for cataract in 3 patients with Mooren ulcer, the period of disease quiescence before surgery was 12 months, 24 months, and 14 months, respectively.5,10 Our previous study11 had a median period of disease inactivity of 4 months. In our current study, the median period of disease inactivity before cataract surgery was 7 months and 61.5% of cases had a quiescent period of 6 months or more. With this protocol followed at our center, the ulcer recurrence rate was low (19%) and no ulcer recurrence occurred in the immediate postoperative period up to 3 months. Hence, maintaining a disease-free interval 6 months or more before considering cataract surgery seems be a valuable guideline to follow, even though this might fall short of a definite protocol considering the small number of cases studied. Extracapsular cataract extraction has been the most commonly reported cataract surgery technique for Mooren ulcer cases. Only 5 cases of phacoemulsification surgery have been reported between 1997 and 2005.5,10,11 Over the years, technology has advanced and cataract surgery techniques have shifted from traditional ECCE to small-incision cataract surgery (SICS) and phacoemulsification, which give all the benefits of a small incision. In our study, 10 eyes had ECCE (38.5%) and 13 eyes had phacoemulsification (50.0%), suggesting a shift toward
Figure 3. Outcomes after cataract surgery. A: Healed Mooren ulcer with nasal patch graft (arrow); posterior chamber intraocular lens (PC IOL) in place; CDVA 20/40. B: Quiescent Mooren ulcer and scarred nasal patch graft; PC IOL in place; CDVA 20/50. C: Healed superior Mooren ulcer; PC IOL in place; CDVA 20/20.
Volume 43 Issue 8 August 2017
1048
CATARACT SURGERY OUTCOMES IN MOOREN ULCER PATIENTS
Figure 4. A: Healed Mooren ulcer with vascularized corneal scar superiorly and visually significant cataract. B: Reactivation of ulcer in temporal quadrant (arrow) occurring 20 months after cataract surgery; the posterior chamber intraocular lens in place.
this trend. However, on analysis, the type of surgery (ECCE, SICS, or phacoemulsification) had no significant influence on ulcer reactivation, indicating that there is no downside to performing a surgical technique of preferred choice and no 1 type of surgery is superior. Although the numbers of cases are too few to draw definite conclusions, these findings might nevertheless be relevant across a broader group while planning cataract surgery. With regard to the surgical incision, it has been proposed that avoiding a clear corneal incision might have a role in preventing ulcer reactivation. This is because the release of corneal stromal antigens during surgery is thought to be responsible for induction of immune response. Gottsch et al.19 have proposed that this can occur from an immune response to calgranulin C, a normally concealed antigen expressed by keratocytes. Based on this principle, a scleral surgical incision was most preferred by the surgeons (n Z 22 [84.6%]) in our study. Previous cataract surgery might have a role in the pathogenesis of Mooren ulcer, by exposure of previously concealed corneal antigens to antigen-presenting cells.2,7,8,20 Acharya et al.20 evaluated 14 cases of Mooren ulcer that had previous ECCE and found that ulcers developed contiguous to the main surgical site in 71% of cases. In our study, of the 5 cases with active ulceration after cataract surgery, 1 case had ulcer occurrence in the quadrant of the main surgical incision; however, this happened
7 years after surgery and is probably not related to surgical trauma. In summary, with adequate immunosuppression and/or surgical treatment of active ulceration, cataract surgery in Mooren ulcer patients is safe to perform and significantly improves visual acuity. Maintaining a disease-free interval for 6 months or more before cataract surgery has favorable outcomes, although this might fall short of a definite protocol to follow, considering the small number of cases studied. The role of maintenance immunosuppression before cataract surgery is not proven. This suggests that continuing immunosuppressive drugs in anticipation of cataract surgery might not be necessary; however, it might be required to keep the disease under control. No significant risk factors for disease recurrence were identified. The type of cataract surgery had no influence on ulcer reactivation, implying that surgeons should not be hesitant in performing surgery of their choice, although the number of cases in this study might be inadequate to draw definite conclusions. A scleral incision has favorable outcomes. Although previous reports assess outcomes in individuals or small groups of patients, this study evaluated a much larger group that had cataract surgery over a 15-year period. In addition, we described various pre-cataract surgery treatments administered for active Mooren ulcer based on severity, analyzed possible risk factors for disease recurrence, assessed the influence of maintenance immunosuppression and disease quiescence, compared different types of cataract surgeries, and described the outcomes after cataract surgery. To our knowledge, the risk factors for postoperative ulcer reactivation and a comparison between cataract surgery types has not been studied previously. Our analysis showed that no significant risk factors could be identified, and a comparison of cataract surgery types did not show predilection to any type in particular. Considering the rarity of this disease, it might be difficult to assess a large cohort. However, our study, which to our knowledge, comprised the largest group of such patients reported to date, should assist surgeons with better
Table 3. Characteristics of the Mooren ulceration recurrence cases after cataract surgery. Initial Ulcer
Cataract Surgery
Ulcer Recurrence
Case
Corneal Quadrant (CH)
Type
Corneal Quadrant
Incision
Corneal Quadrant
Time (Mo)
Management
Final CDVA
1
Nasal, inferior (5)
ECCE
Superior
Scleral
Inferior
21
20/80
2 3
Nasal (5) Nasal, inferior, temporal (8)
ECCE Phaco
Superior Superior
Scleral Scleral
Temporal Nasal
3 8
4
Superior, nasal, inferior (8) Nasal, inferior, temporal (10)
Phaco
Superotemporal
Scleral
20 & 48
Phaco
Superior
Scleral
Temporal (twice) Superior
Topical plus oral steroids, oral imms Topical steroids, CR-TABCL Topical plus oral plus IV Steroids, oral plus IV imms, CR-TABCL Topical plus oral plus IV steroids, oral plus IV imms, CR-TABCL Topical plus oral steroids, CR-TABCL
5
84
20/100 20/252
20/50 20/320
CDVA Z corrected distance visual acuity; CH Z clock hours; CR-TABCL Z conjunctival resection, tissue adhesive with bandage contact lens; ECCE Z extracapsular cataract extraction; imms Z immunosuppressants (nonsteroidal); IV Z intravenous; Phaco Z phacoemulsification surgery
Volume 43 Issue 8 August 2017
CATARACT SURGERY OUTCOMES IN MOOREN ULCER PATIENTS
Table 4. Univariate analyses of factors considered for association with Mooren ulcer recurrence after cataract surgery. Factor Laterality of ulcer Clock hours of peripheral corneal ulceration Maintenance immunosuppression Period of disease inactivity before cataract surgery Type of cataract surgery Duration of postoperative immunosuppression
P Value .22 .72 .055 .83 .66 .19
planning of cataract surgery in patients with Mooren ulcer. Studying the role of immunosuppression, importance of disease quiescence, and influence of cataract surgery type is important to understand the chance for surgical success and visual outcomes in such patients. An apprehension that cataract surgery will influence ulcer pathogenesis should not prevent surgeons from visually rehabilitating this group of patients.
WHAT WAS KNOWN For patients with Mooren ulcer, cataract surgery is safe to perform in quiet noninflamed eyes. Assessments of possible risk factors for postoperative ulcer reactivation and comparisons between cataract surgery types have not been performed.
WHAT THIS PAPER ADDS Cataract surgery outcomes analyzed in 26 patients with Mooren ulcer studied indicate favorable results with a preoperative disease-free interval of 6 months or more with immunosuppression and/or surgical treatment. A risk-factor analysis for postoperative ulcer reactivation did not identify significant risks. A comparison of cataract surgery types showed no predilection to a particular type.
REFERENCES 1. Moorens A. Ulcus Rodens. Ophthalmiatrische Beobachtungen. Berlin, August Hirschwald, 1867; 107–110 2. Joondeph HC, McCarthy WL Jr, Rabb M, Constantaras AA. Mooren’s ulcer: two cases occurring after cataract extraction and treated with hydrophilic lens. Ann Ophthalmol 1976; 8:187–194 3. Watson PG. Management of Mooren’s ulceration. Eye 1997; 11:349–356. Available at: https://www.nature.com/eye/journal/v11/n3/pdf/eye199774a. pdf. Accessed June 21, 2017 4. Garg P, Sangwan VS. Mooren’s ulcer. In: Krachmer JH, Mannis MJ, Holland EJ, eds, Cornea; Fundamentals, Diagnosis and Management, 3d ed. Saint Louis, MO, Mosby Elsevier, 2010; 1149–1153 5. Akova YA, Aslan BS, Duman S. Phacoemulsification and intraocular lens implantation in a patient with Mooren’s ulcer. Ophthalmic Surg Lasers 1997; 28:769–771
1049
6. Chen J, Xie H, Wang Z, Yang B, Liu Z, Chen L, Gong X, Lin Y. Mooren’s ulcer in China: a study of clinical characteristics and treatment. Br J Ophthalmol 2000; 84:1244–1249. Available at: https://www.ncbi.nlm.nih.gov/pmc /articles/PMC1723298/pdf/v084p01244.pdf. Accessed June 21, 2017 7. Kafkala C, Choi J, Zafirakis P, Baltatzis S, Livir-Rallatos C, Rojas B, Foster CS. Mooren ulcer; an immunopathologic study. Cornea 2006; 25:667–673 8. Zegans M, Srinivasan M, McHugh T, Whitcher JP, Margolis TP, Lietman T, Jennette JC, Cunningham ET Jr. Mooren ulcer in South India: serology and clinical risk factors. Am J Ophthalmol 1999; 128:205–210 9. Hirano J. Surgery for cataract in Mooren’s ulcer. Jpn J Ophthalmol 1979; 23:265–271 10. Watanabe H, Katakami C, Tsukahara Y, Negi A. Cataract surgery in patients with advanced Mooren’s ulcer. Jpn J Ophthalmol 2001; 45:543–546 11. Sangwan VS, Surender P, Burman S. Cataract surgery in patients with Mooren’s ulcer. J Cataract Refract Surg 2005; 31:359–362. Available at: http://www.unisinucartagena.edu.co/biblioteca/oftalmologia/REVISION_ TEMA/SEGMENTO_ANTERIOR/CATARATA/CATARATA_ADULTO/ARTI CULOS/Caratata_y_UlceradeMooren.pdf. Accessed June 21, 2017 12. Ashar JN, Mathur A, Sangwan VS. Immunosuppression for Mooren’s ulcer: evaluation of the stepladder approachdtopical, oral and intravenous immunosuppressive agents. Br J Ophthalmol 2013; 97:1391–1394 13. Srinivasan M, Zegans ME, Joseph R, Zelefsky JR, Kundu A, Lietman T, Whitcher JP, Cunningham ET Jr. Clinical characteristics of Mooren’s ulcer in South India. Br J Ophthalmol 2007; 91:570–575. Available at: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC1954782/pdf/570.pdf. Accessed June 21, 2017 14. Zelefsky JR, Srinivasan M, Kundu A, Lietman T, Whitcher JP, Wang K, Buyse M, Cunningham ET Jr. Hookworm infestation as a risk factor for Mooren’s ulcer in South India. Ophthalmology 2007; 114:450–453 15. Brown SI. Mooren’s ulcer; histopathology and proteolytic enzymes of adjacent conjunctiva. Br J Ophthalmol 1975; 59:670–674. Available at: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC1017431/pdf/brjopthal00263 -0065.pdf. Accessed June 21, 2017 16. Berkowitz PJ, Arentsen JJ, Felberg NT, Laibson PR. Presence of circulating immune complexes in patients with peripheral corneal disease. Arch Ophthalmol 1983; 101:242–245 17. Brown SI, Mondino BJ, Rabin BS. Autoimmune phenomenon in Mooren’s ulcer. Am J Ophthalmol 1976; 82:835–840 18. Brown SI, Mondino BJ. Therapy of Mooren’s ulcer. Am J Ophthalmol 1984; 98:1–6 19. Gottsch JD, Li Q, Ashraf F, O’Brien TP, Startk WJ, Liu SH. Cytokineinduced calgranulin C expression inkeratocytes. Clin Immunol 1999; 91:34–40 20. Acharya NR, Srinivasan M, Kundu A, Lietman TM, Whitcher JP, Cunningham ET Jr. Mooren’s ulcer following extracapsular cataract extraction. Eur J Ophthalmol 2008; 18:351–355. Available at: http:// www.aravind.org/content/aravindnews/pdffiles/june082.pdf. Accessed June 21, 2017
Disclosure: None of the authors has a financial or proprietary interest in any material or method mentioned.
First author: Shilpa Das, MS Prof. Brien Holden Eye Research Centre, L.V. Prasad Eye Institute, Hyderabad, Telangana, India
Volume 43 Issue 8 August 2017
ARTICLE
Clinical course and outcomes in patients with Mooren ulcer who had cataract surgery Shilpa Das, MS, Ashik Mohamed, MTech, Virender S. Sangwan, MS
Purpose: To report outcomes of cataract surgery in patients with Mooren ulcer.
Setting: L.V. Prasad Eye Institute, Hyderabad, India. Design: Retrospective case series. Methods: The medical records of patients with Mooren ulcer who had cataract surgery between 2000 and 2015 were assessed. The main outcome measures were the role of preoperative immunosuppression and disease inactivity, cataract surgery safety, visual outcomes, and postoperative ulcer recurrence. Results: Of 22 patients (26 eyes), the mean corneal ulceration was 6.8 clock hours G 2.9 (SD). Corticosteroids were the most commonly used (84.6% of the 26 eyes) preoperative immunosuppression agents and 38.5% of the 26 eyes were under maintenance immunosuppression. The median disease inactivity before surgery was 7 months. Cataract surgery was extracapsular in 10 patients, small incision in 3 patients, and phacoemulsification in 13 patients.
M
ooren ulcer, a noninfectious idiopathic peripheral ulcerative keratitis, is an autoimmune disorder characterized by painful ulceration of the peripheral cornea. Since its initial description by Albert Mooren in 1867,1 several clinicians have studied its pathogenesis and manifestations, and highlighted various treatment modalities. The disease has a chronic course characterized by exacerbations and remissions.2 The main modality of management is local and systemic immunosuppression.3 In addition, surgical modalities, such as conjunctival resection, tissue adhesives, patch grafts, and lamellar and penetrating keratoplasty (PKP), have been advocated for management of this disease.4 Sequelae secondary to the keratitis, such as corneal scarring, irregular corneal contour, iridocorneal synechiae, secondary glaucoma, and complicated
Twenty-two eyes had scleral incisions. The median follow-up was 6 months (interquartile range, 10 months). The median corrected distance visual acuity (CDVA) improved from 1.48 logarithm of minimum angle of resolution (logMAR) before surgery to 0.30 and 0.35 logMAR at 1 month and at the last follow-up after surgery, respectively (P % .0001). Mooren ulcer recurred in 5 eyes between 3 months and 7 years after surgery. No disease activity was seen in the immediate postoperative period. No significant risk factors for disease recurrence were noted.
Conclusions: With adequate immunosuppression, cataract surgery in eyes with Mooren ulcer was safe and CDVA improved significantly with no disease reactivation immediately after surgery. No proven role of maintenance immunosuppression was observed. The type of cataract surgery had no influence on ulcer reactivation. Patients with a disease-free interval of 6 months or more before surgery and those who had scleral incisions had favorable outcomes. J Cataract Refract Surg 2017; 43:1044–1049 Q 2017 ASCRS and ESCRS
cataract, can cause significant visual impairment even if the active disease resolves. Cataract surgery for complicated or senile cataract in these patients is a decision that often needs to be made in the clinic. It has been proposed that surgical trauma such as that from keratoplasty or cataract surgery itself, if performed during the active phase of the disease, can cause reactivation or worsening of ulceration.5,6 In addition, studies have shown that previous corneal trauma or surgery might have a role in the pathogenesis of Mooren ulcer in a previously uninvolved eye by exposure of concealed corneal antigens to antigen-presenting cells, resulting in intense infiltration of lymphocytes.7,8 Hence, important aspects to watch for are the timing of cataract surgery as well as the occurrence or recurrence or worsening of ulceration after cataract surgery.
Submitted: December 9, 2016 | Final revision submitted: May 7, 2017 | Accepted: May 21, 2017 From the Prof. Brien Holden Eye Research Centre (Das), Ophthalmic Biophysics (Mohamed), and the Cornea, Ocular Immunology and Uveitis Service, L.V. Prasad Eye Institute, Hyderabad, Telangana, India. Corresponding author: Virender S. Sangwan, MS (Ophthalmology), Cornea, Ocular Immunology and Uveitis Service, L.V. Prasad Eye Institute, L.V. Prasad Marg, Road No.2, Banjara hills, Hyderabad-500034, Telangana, India. E-mail: [email protected]. Q 2017 ASCRS and ESCRS Published by Elsevier Inc.
0886-3350/$ - see frontmatter http://dx.doi.org/10.1016/j.jcrs.2017.05.034
1045
CATARACT SURGERY OUTCOMES IN MOOREN ULCER PATIENTS
From earlier reports of outcomes of cataract surgery in patients with Mooren ulcer, much of what is known has been gleaned from isolated case reports and small case series.5,9,10 We previously reported outcomes of cataract surgery in 6 eyes with Mooren ulcer from our center.11 In the current study, we assessed a much larger cohort of this relatively rare group of patients to evaluate the effect of immunosuppression, disease inactivity, and type of cataract surgery on the postoperative outcomes.
Table 1. Distribution of eyes with Mooren ulcer by peripheral corneal involvement. Involvement %3 clock hours O3–6 clock hours O6–9 clock hours O9–12 clock hours
Eyes (n) 3 12 6 5
documented at 3, 6, 12, 18, and 24 months and at each patient’s last visit after cataract surgery.
PATIENTS AND METHODS Study Design and Patients In this retrospective study, the medical records of all patients diagnosed with Mooren ulcer who had cataract surgery between January 2000 and August 2015 at L.V. Prasad Eye Institute, Hyderabad, India, were reviewed. Institutional Review Board approval was obtained (LEC number 12-15-129). The diagnosis of Mooren ulcer was based on the characteristic clinical features of crescentshaped peripheral corneal ulcer with overhanging margins, cellular infiltration at the advancing edge, circumferential spread, no scleral involvement, and absence of associated systemic disease.4 The research methods adhered to the tenets of the Declaration of Helsinki. Preoperative Data Assessment The clinical information analyzed included preoperative data such as visual acuity, pattern of ulceration, type and duration of immunosuppressive therapy, surgical management for active ulceration, and period of disease inactivity. To describe ulcer location and extent, the peripheral cornea was divided into 4 quadrants and 12 clock hours. The superior quadrant spanned from clock hours 10:30 to 1:30, the inferior from 4:30 to 7:30, the nasal from 1:30 to 4:30, and the temporal from 7:30 to 10:30. (For nasal and temporal quadrants, clock hours were exchanged depending on the eye involved.) Bilateral cases were treated as independent data. Based on clinical presentation, tailored therapy with topical and systemic immunosuppression was given to patients in accordance with the severity-based stepladder approach.12 This depended on ulcer laterality, corneal quadrants involved, stromal loss, and presence of perforation. The various drugs used for immunosuppression included topical, oral or intravenous steroids (prednisolone or methyl prednisolone), and oral or intravenous immunosuppressants (folic acid analogs, antimetabolites, or alkylating agents). Surgical treatment included conjunctival resection, tissue adhesives, and corneal patch grafts, when indicated. Intraoperative Data Assessment The indication for cataract surgery in these patients was significant visual impairment because of cataract, assessed by slitlamp examination. Surgery was performed after complete resolution of active disease, and surgery type as well as site was individualized based on the grade of cataract and area of peripheral corneal involvement. The area of previous ulceration or thinning was avoided as much as possible. Site, incision, and type of cataract surgery performed were documented. Postoperative Data Assessment Postoperatively, all patients received prednisolone acetate 1.0% eyedrops for a minimum of 6 weeks in weekly tapering doses, starting with a frequency of 6 times per day with antibiotic drops 4 times a day for 1 week. The postoperative follow-up included at least a minimum of 3 evaluations (1 day, 1 week, and 5 weeks) for each patient (except 1 patient who was lost to follow-up after 1 week). Thereafter, visual acuity and signs of ulcer recurrence were
Statistical Analysis Statistical analysis was performed using the statistical software Origin (version 7.0, Origin Lab Corp.). Continuous data were checked for normality using the Shapiro-Wilk test and were described using mean and standard deviation (parametric data) or median and interquartile range (IQR) (nonparametric data). The variances between 2 datasets were checked for equality using the Levene test. The independent t test (independent samples) and paired t test (nonindependent samples) were used to compare parametric data with equal variance. The Mann-Whitney test (independent samples) and Wilcoxon signed-rank test (nonindependent samples) were used to compare parametric data with unequal variance and nonparametric data. The Fisher exact test was used to compare the categorical data. A P value of 0.05 or less was considered statistically significant.
RESULTS Patient Demographics and Disease Pattern
A total of 281 patients diagnosed with Mooren ulcer were seen between 2000 and 2015, of whom 22 patients (26 eyes) had cataract surgery; the cataract surgery rate was 7.8%. In the cohort of 22 patients, the median age at presentation was 62.5 years (IQR, 25) and male-to-female ratio was 17:5. Five patients (22.7%) had unilateral Mooren ulcer and 17 patients (77.3%) had bilateral ulceration, of whom 4 patients had cataract surgery in both eyes. A mean of 6.8 clock hours G 2.9 (SD) (range 2 to 12 clock hours) of peripheral corneal ulceration was seen at presentation. Table 1 shows the distribution of Mooren ulcer in various clock hours of the peripheral cornea. The inferior quadrant of the peripheral cornea was most commonly involved (23 eyes, 89%) followed by nasal (20 eyes, 77%). Treatment
Twenty-two eyes received medical treatment and 20 eyes received both medical and surgical treatment to control ulcer activity before the cataract surgery. In 4 cases, the disease was inactive at presentation. Corticosteroids (topical and/or systemic) were the most commonly used (n Z 22 [84.6%]) for pre-cataract surgery immunosuppression. The combination of topical and oral steroids was the most used immunosuppression treatment of choice (31% [n Z 8]). The median duration of immunosuppression before cataract surgery was 6.8 months (IQR, 15.5). Figure 1 shows the distribution of preoperative immunosuppression therapy. Table 2 shows the surgical treatment the patients received before cataract surgery. The median period of disease inactivity before cataract surgery was Volume 43 Issue 8 August 2017
1046
CATARACT SURGERY OUTCOMES IN MOOREN ULCER PATIENTS
Figure 1. Preoperative immunosuppression distribution in patients with Mooren ulcer (IV Z intravenous).
7 months (IQR, 22), and 16 cases (61.5%) had a quiescent period of 6 months or more. Just before cataract surgery, 10 (38.5%) of the 26 eyes were under maintenance immunosuppression (10 topical; 4 topical and systemic), given selectively to control active disease. Cataract Surgery and Postoperative Course
Patients had different varieties of cataract surgery, incision type, and surgical site distribution. Areas of previous ulceration/thinning were avoided as much as possible. In 8 of 26 eyes, placement of the surgical incision close to an area of previous ulceration was unavoidable because of the nearly total extent of peripheral involvement. Ten patients (38.5%) had extracapsular cataract extraction (ECCE), 3 patients (11.5%) had small-incision cataract surgery (SICS), and 13 patients (50.0%) had phacoemulsification surgery. Twenty-two eyes (84.6%) had a scleral incision. The median follow-up after surgery was 6 months (IQR, 20). Patients received immunosuppression treatment after cataract surgery for a median of 6 weeks (IQR, 3), with a total range of 1 week to 12.4 years. In addition to the 6-week regimen of topical prednisolone acetate 1.0% eyedrops given to all patients, 4 patients received oral steroids (prednisolone 1 mg/kg a day, gradually tapered) and 1 patient received additional oral immunosuppressants (azathioprine 100 mg a day in divided doses) because of a greater severity of the initial ulceration. Visual Acuity
The mean corrected distance visual acuity (CDVA) at presentation was 0.78 G 0.55 logarithm of the minimum angle of resolution (logMAR) (range 0.00 to 2.09 logMAR). The median CDVA significantly improved after cataract
Table 2. Treatment before cataract surgery. Treatment 1. None 2. Conjunctival resection plus tissue adhesive 3. Patch graft 4. Both (2) and (3)
Volume 43 Issue 8 August 2017
Eyes, n (%) 6 (23.1) 16 (61.5) 3 (11.5) 1 (3.9)
surgery at 1 month and at the last follow-up (both P Z .0001). Figure 2 compares the CDVA preoperatively and postoperatively. The CDVA improved in all patients after cataract surgery except 2, the first patient had graft failure after PKP that was performed after cataract surgery and the second had central corneal scarring. Figure 3 shows postoperative outcomes in 3 patients. Ulcer Reactivation
Active ulceration recurred in 5 eyes (19.2%) between 3 months and 7 years after cataract surgery; they were appropriately managed. Figure 4 shows Mooren ulcer reactivation in a patient after cataract surgery. No recurrences were seen in the immediate postoperative period. Table 3 shows the characteristics of the recurrence cases. No statistically significant association was found between the possible risk factors and recurrence of active ulceration after cataract surgery (Table 4). DISCUSSION Mooren ulcer is a persistent peripheral ulcerative keratitis with a chronic course and repeated bouts of inflammation.3 It has varied manifestations with respect to age, sex, laterality, and severity of condition. The demographics vary in different parts of the world. In the southern part of India, studies have shown male preponderance with an average age of presentation between 50 and 65 years.8,12–14 The sex and age distribution in our patients were similar. Considerable evidence supports the notion that Mooren ulcer is an autoimmune disorder.15 Patients with this disease have infiltrating leucocytes in corneal specimens, as well as circulating immune complexes to stromal antigens.16,17 Immunosuppression is the main modality of treatment of Mooren ulcer.18 The various drugs used for immunosuppression in our patients included topical, oral or intravenous steroids (prednisolone or methyl prednisolone), and oral or intravenous immunosuppressives (folic acid analogs, antimetabolites, or alkylating agents). Based on our experience, the immunosuppression regimen in this study followed a stepladder approach as per ulcer severity. This depended on ulcer laterality, corneal
CATARACT SURGERY OUTCOMES IN MOOREN ULCER PATIENTS
Figure 2. Significant improvement in CDVA after cataract surgery at 1 month (Month1) and at each patient’s last visit (Final) compared with before cataract surgery (Pre) CDVA (CDVA Z corrected distance visual acuity; IQR Z interquartile range; logMAR Z logarithm of the minimum angle of resolution).
quadrants involved, stromal loss, and the presence of perforation (described previously by our group12). The most common treatment received by our patients was a combination of oral steroids and topical steroids (approximately one third of patients). With adequate immunosuppression, all ulcers healed. For any autoimmune disease with multiple exacerbations despite primary treatment, the principle of immunosuppressive regimen is to keep patients on a minimum dose maintenance therapy that will suppress the disease process. Indiscriminate use of immunosuppressives can cause unwanted side effects. To our knowledge, no studies to date have analyzed the role of maintenance immunosuppressive therapy in preventing recurrent inflammation in Mooren ulcer cases. The role of such therapy becomes more crucial to ascertain if cataract surgery is being planned in these patients given the evidence that surgery itself can trigger inflammation.7,8 Furthermore, some surgeons might believe that administering additional prophylactic immunosuppressives before surgery in anticipation of inflammation might be useful. Of the studies of cataract surgery in patients with Mooren ulcer thus far, 1 case report described the use of low-dose immunosuppression (oral cyclophosphamide)
1047
until cataract surgery and the addition of immunosuppressives (oral steroids) 1 day before surgery.5 In our study, 10 of 26 cases were on selective low-dose maintenance immunosuppression before cataract surgery (6 eyes on topical; 4 eyes on topical and systemic) and no additional immunosuppressives were introduced before surgery. Of the 5 patients who had ulcer recurrence in our study, 4 belonged to this category (P Z 0.055, univariate analysis assessing correlation). This might suggest that the disease severity was greater in these patients and the recurrence of active ulceration was inevitable. Alternatively, one might propose that maintenance immunosuppressive therapy provided no benefit toward preventing ulcer reactivation. We might hypothesize that although immunosuppressives are required (primary and maintenance) to keep the disease quiescent, there is no proof that maintenance or additive immunosuppressive therapy before cataract surgery plays a role in the prevention of ulcer reactivation. However, further studies are needed to validate this hypothesis. In general, the eye of any patient should be quiet before cataract surgery is performed. In 2 studies of phacoemulsification surgery for cataract in 3 patients with Mooren ulcer, the period of disease quiescence before surgery was 12 months, 24 months, and 14 months, respectively.5,10 Our previous study11 had a median period of disease inactivity of 4 months. In our current study, the median period of disease inactivity before cataract surgery was 7 months and 61.5% of cases had a quiescent period of 6 months or more. With this protocol followed at our center, the ulcer recurrence rate was low (19%) and no ulcer recurrence occurred in the immediate postoperative period up to 3 months. Hence, maintaining a disease-free interval 6 months or more before considering cataract surgery seems be a valuable guideline to follow, even though this might fall short of a definite protocol considering the small number of cases studied. Extracapsular cataract extraction has been the most commonly reported cataract surgery technique for Mooren ulcer cases. Only 5 cases of phacoemulsification surgery have been reported between 1997 and 2005.5,10,11 Over the years, technology has advanced and cataract surgery techniques have shifted from traditional ECCE to small-incision cataract surgery (SICS) and phacoemulsification, which give all the benefits of a small incision. In our study, 10 eyes had ECCE (38.5%) and 13 eyes had phacoemulsification (50.0%), suggesting a shift toward
Figure 3. Outcomes after cataract surgery. A: Healed Mooren ulcer with nasal patch graft (arrow); posterior chamber intraocular lens (PC IOL) in place; CDVA 20/40. B: Quiescent Mooren ulcer and scarred nasal patch graft; PC IOL in place; CDVA 20/50. C: Healed superior Mooren ulcer; PC IOL in place; CDVA 20/20.
Volume 43 Issue 8 August 2017
1048
CATARACT SURGERY OUTCOMES IN MOOREN ULCER PATIENTS
Figure 4. A: Healed Mooren ulcer with vascularized corneal scar superiorly and visually significant cataract. B: Reactivation of ulcer in temporal quadrant (arrow) occurring 20 months after cataract surgery; the posterior chamber intraocular lens in place.
this trend. However, on analysis, the type of surgery (ECCE, SICS, or phacoemulsification) had no significant influence on ulcer reactivation, indicating that there is no downside to performing a surgical technique of preferred choice and no 1 type of surgery is superior. Although the numbers of cases are too few to draw definite conclusions, these findings might nevertheless be relevant across a broader group while planning cataract surgery. With regard to the surgical incision, it has been proposed that avoiding a clear corneal incision might have a role in preventing ulcer reactivation. This is because the release of corneal stromal antigens during surgery is thought to be responsible for induction of immune response. Gottsch et al.19 have proposed that this can occur from an immune response to calgranulin C, a normally concealed antigen expressed by keratocytes. Based on this principle, a scleral surgical incision was most preferred by the surgeons (n Z 22 [84.6%]) in our study. Previous cataract surgery might have a role in the pathogenesis of Mooren ulcer, by exposure of previously concealed corneal antigens to antigen-presenting cells.2,7,8,20 Acharya et al.20 evaluated 14 cases of Mooren ulcer that had previous ECCE and found that ulcers developed contiguous to the main surgical site in 71% of cases. In our study, of the 5 cases with active ulceration after cataract surgery, 1 case had ulcer occurrence in the quadrant of the main surgical incision; however, this happened
7 years after surgery and is probably not related to surgical trauma. In summary, with adequate immunosuppression and/or surgical treatment of active ulceration, cataract surgery in Mooren ulcer patients is safe to perform and significantly improves visual acuity. Maintaining a disease-free interval for 6 months or more before cataract surgery has favorable outcomes, although this might fall short of a definite protocol to follow, considering the small number of cases studied. The role of maintenance immunosuppression before cataract surgery is not proven. This suggests that continuing immunosuppressive drugs in anticipation of cataract surgery might not be necessary; however, it might be required to keep the disease under control. No significant risk factors for disease recurrence were identified. The type of cataract surgery had no influence on ulcer reactivation, implying that surgeons should not be hesitant in performing surgery of their choice, although the number of cases in this study might be inadequate to draw definite conclusions. A scleral incision has favorable outcomes. Although previous reports assess outcomes in individuals or small groups of patients, this study evaluated a much larger group that had cataract surgery over a 15-year period. In addition, we described various pre-cataract surgery treatments administered for active Mooren ulcer based on severity, analyzed possible risk factors for disease recurrence, assessed the influence of maintenance immunosuppression and disease quiescence, compared different types of cataract surgeries, and described the outcomes after cataract surgery. To our knowledge, the risk factors for postoperative ulcer reactivation and a comparison between cataract surgery types has not been studied previously. Our analysis showed that no significant risk factors could be identified, and a comparison of cataract surgery types did not show predilection to any type in particular. Considering the rarity of this disease, it might be difficult to assess a large cohort. However, our study, which to our knowledge, comprised the largest group of such patients reported to date, should assist surgeons with better
Table 3. Characteristics of the Mooren ulceration recurrence cases after cataract surgery. Initial Ulcer
Cataract Surgery
Ulcer Recurrence
Case
Corneal Quadrant (CH)
Type
Corneal Quadrant
Incision
Corneal Quadrant
Time (Mo)
Management
Final CDVA
1
Nasal, inferior (5)
ECCE
Superior
Scleral
Inferior
21
20/80
2 3
Nasal (5) Nasal, inferior, temporal (8)
ECCE Phaco
Superior Superior
Scleral Scleral
Temporal Nasal
3 8
4
Superior, nasal, inferior (8) Nasal, inferior, temporal (10)
Phaco
Superotemporal
Scleral
20 & 48
Phaco
Superior
Scleral
Temporal (twice) Superior
Topical plus oral steroids, oral imms Topical steroids, CR-TABCL Topical plus oral plus IV Steroids, oral plus IV imms, CR-TABCL Topical plus oral plus IV steroids, oral plus IV imms, CR-TABCL Topical plus oral steroids, CR-TABCL
5
84
20/100 20/252
20/50 20/320
CDVA Z corrected distance visual acuity; CH Z clock hours; CR-TABCL Z conjunctival resection, tissue adhesive with bandage contact lens; ECCE Z extracapsular cataract extraction; imms Z immunosuppressants (nonsteroidal); IV Z intravenous; Phaco Z phacoemulsification surgery
Volume 43 Issue 8 August 2017
CATARACT SURGERY OUTCOMES IN MOOREN ULCER PATIENTS
Table 4. Univariate analyses of factors considered for association with Mooren ulcer recurrence after cataract surgery. Factor Laterality of ulcer Clock hours of peripheral corneal ulceration Maintenance immunosuppression Period of disease inactivity before cataract surgery Type of cataract surgery Duration of postoperative immunosuppression
P Value .22 .72 .055 .83 .66 .19
planning of cataract surgery in patients with Mooren ulcer. Studying the role of immunosuppression, importance of disease quiescence, and influence of cataract surgery type is important to understand the chance for surgical success and visual outcomes in such patients. An apprehension that cataract surgery will influence ulcer pathogenesis should not prevent surgeons from visually rehabilitating this group of patients.
WHAT WAS KNOWN For patients with Mooren ulcer, cataract surgery is safe to perform in quiet noninflamed eyes. Assessments of possible risk factors for postoperative ulcer reactivation and comparisons between cataract surgery types have not been performed.
WHAT THIS PAPER ADDS Cataract surgery outcomes analyzed in 26 patients with Mooren ulcer studied indicate favorable results with a preoperative disease-free interval of 6 months or more with immunosuppression and/or surgical treatment. A risk-factor analysis for postoperative ulcer reactivation did not identify significant risks. A comparison of cataract surgery types showed no predilection to a particular type.
REFERENCES 1. Moorens A. Ulcus Rodens. Ophthalmiatrische Beobachtungen. Berlin, August Hirschwald, 1867; 107–110 2. Joondeph HC, McCarthy WL Jr, Rabb M, Constantaras AA. Mooren’s ulcer: two cases occurring after cataract extraction and treated with hydrophilic lens. Ann Ophthalmol 1976; 8:187–194 3. Watson PG. Management of Mooren’s ulceration. Eye 1997; 11:349–356. Available at: https://www.nature.com/eye/journal/v11/n3/pdf/eye199774a. pdf. Accessed June 21, 2017 4. Garg P, Sangwan VS. Mooren’s ulcer. In: Krachmer JH, Mannis MJ, Holland EJ, eds, Cornea; Fundamentals, Diagnosis and Management, 3d ed. Saint Louis, MO, Mosby Elsevier, 2010; 1149–1153 5. Akova YA, Aslan BS, Duman S. Phacoemulsification and intraocular lens implantation in a patient with Mooren’s ulcer. Ophthalmic Surg Lasers 1997; 28:769–771
1049
6. Chen J, Xie H, Wang Z, Yang B, Liu Z, Chen L, Gong X, Lin Y. Mooren’s ulcer in China: a study of clinical characteristics and treatment. Br J Ophthalmol 2000; 84:1244–1249. Available at: https://www.ncbi.nlm.nih.gov/pmc /articles/PMC1723298/pdf/v084p01244.pdf. Accessed June 21, 2017 7. Kafkala C, Choi J, Zafirakis P, Baltatzis S, Livir-Rallatos C, Rojas B, Foster CS. Mooren ulcer; an immunopathologic study. Cornea 2006; 25:667–673 8. Zegans M, Srinivasan M, McHugh T, Whitcher JP, Margolis TP, Lietman T, Jennette JC, Cunningham ET Jr. Mooren ulcer in South India: serology and clinical risk factors. Am J Ophthalmol 1999; 128:205–210 9. Hirano J. Surgery for cataract in Mooren’s ulcer. Jpn J Ophthalmol 1979; 23:265–271 10. Watanabe H, Katakami C, Tsukahara Y, Negi A. Cataract surgery in patients with advanced Mooren’s ulcer. Jpn J Ophthalmol 2001; 45:543–546 11. Sangwan VS, Surender P, Burman S. Cataract surgery in patients with Mooren’s ulcer. J Cataract Refract Surg 2005; 31:359–362. Available at: http://www.unisinucartagena.edu.co/biblioteca/oftalmologia/REVISION_ TEMA/SEGMENTO_ANTERIOR/CATARATA/CATARATA_ADULTO/ARTI CULOS/Caratata_y_UlceradeMooren.pdf. Accessed June 21, 2017 12. Ashar JN, Mathur A, Sangwan VS. Immunosuppression for Mooren’s ulcer: evaluation of the stepladder approachdtopical, oral and intravenous immunosuppressive agents. Br J Ophthalmol 2013; 97:1391–1394 13. Srinivasan M, Zegans ME, Joseph R, Zelefsky JR, Kundu A, Lietman T, Whitcher JP, Cunningham ET Jr. Clinical characteristics of Mooren’s ulcer in South India. Br J Ophthalmol 2007; 91:570–575. Available at: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC1954782/pdf/570.pdf. Accessed June 21, 2017 14. Zelefsky JR, Srinivasan M, Kundu A, Lietman T, Whitcher JP, Wang K, Buyse M, Cunningham ET Jr. Hookworm infestation as a risk factor for Mooren’s ulcer in South India. Ophthalmology 2007; 114:450–453 15. Brown SI. Mooren’s ulcer; histopathology and proteolytic enzymes of adjacent conjunctiva. Br J Ophthalmol 1975; 59:670–674. Available at: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC1017431/pdf/brjopthal00263 -0065.pdf. Accessed June 21, 2017 16. Berkowitz PJ, Arentsen JJ, Felberg NT, Laibson PR. Presence of circulating immune complexes in patients with peripheral corneal disease. Arch Ophthalmol 1983; 101:242–245 17. Brown SI, Mondino BJ, Rabin BS. Autoimmune phenomenon in Mooren’s ulcer. Am J Ophthalmol 1976; 82:835–840 18. Brown SI, Mondino BJ. Therapy of Mooren’s ulcer. Am J Ophthalmol 1984; 98:1–6 19. Gottsch JD, Li Q, Ashraf F, O’Brien TP, Startk WJ, Liu SH. Cytokineinduced calgranulin C expression inkeratocytes. Clin Immunol 1999; 91:34–40 20. Acharya NR, Srinivasan M, Kundu A, Lietman TM, Whitcher JP, Cunningham ET Jr. Mooren’s ulcer following extracapsular cataract extraction. Eur J Ophthalmol 2008; 18:351–355. Available at: http:// www.aravind.org/content/aravindnews/pdffiles/june082.pdf. Accessed June 21, 2017
Disclosure: None of the authors has a financial or proprietary interest in any material or method mentioned.
First author: Shilpa Das, MS Prof. Brien Holden Eye Research Centre, L.V. Prasad Eye Institute, Hyderabad, Telangana, India
Volume 43 Issue 8 August 2017
