Severity of Pediatric Blepharokeratoconjunctivitis in Asian Eyes.docx

P Severity of Pediatric Blepharokeratoconjunctivitis in Asian Eyes LIVIA TEO, JODHBIR S. MEHTA, HLA M. HTOON, AND DONALD T.H. TAN PURPOSE: To describe and evaluate the severity of pediatric blepharokeratoconjunctivitis in Asia. DESIGN: Retrospective case series. METHODS: Clinical records of patients diagnosed with pediatric blepharokeratoconjunctivitis at a tertiary refer- ral center in Singapore from 1991 through 2010 were reviewed. Patients were graded as having mild (corneal involvement without scarring), moderate (corneal scar- ring), or severe (corneal scarring with thinning or perfo- ration) disease based on recorded clinical findings. RESULTS: Fifty-one patients were diagnosed with pedi- atric blepharokeratoconjunctivitis. The mean age at pre- sentation was 10.2 3.6 years, most patients were female (80.4%), and the mean duration of follow-up was 58.9 44.0 months. Chinese (56.9%) subjects made up most of the cases. Most subjects had moderate (56.9%), followed by severe (37.4%) and mild (5.9%), disease. Four patients (7.9%) had an associated dermatologic disease. All patients were treated with topical antibiotics, and 98% were treated with topical steroids. Nineteen (37.3%) patients received systemic antibiotic therapy, and 1 received systemic steroid therapy. Three patients required deep lamellar keratoplasty (2 tectonic and 1 optical), and 2 underwent cornea gluing alone; all 5 of them were Chinese. Patients graded as having severe disease were more likely to undergo surgical intervention (26.3%) than patients who were graded as having mod- erate (0%) and mild (0%) disease (P < .05). The main complication of treatment was raised intraocular pressure in 7 (13.7%) patients requiring medical therapy. Overall, best-corrected visual acuity improved by 0.10 logarithm can arrest the disease process and can minimize visual morbidity. (Am J Ophthalmol 2012;153:564 570. © 2012 by Elsevier Inc. All rights reserved.) EDIATRIC BLEPHAROKERATOCONJUNCTIVITIS IS AN underrecognized and poorly defined syndrome.1 It is associated frequently with a delay between disease and presentation. Jones and associates demonstrated that a 2-year lag between disease onset and presentation can result in a 0.06 logarithm of the minimal angle of resolu- tion (logMAR)-unit reduction in visual acuity (P .054),2 which highlights that the disease can result in significant visual morbidity. The management of pediatric blepharokeratoconjuncti- vitis can be challenging. Currently, there is a lack of an effective, standardized treatment regimen for the disease, with potentially sight-threatening complications like am- blyopia, thinning, and perforation and treatment-related complications such as steroid-induced glaucoma and cata- racts.2,3 Because this disease usually begins early in life, the lifelong burden of the disease also can affect the quality of life of the patient. Previous studies have described the clinical spectrum, management, and visual outcomes of the disease, and attempts have been made to grade the disease.2,4 8 How- ever, most studies have had small sample sizes with nonstandardized treatments and evaluations. The purpose of our study was to describe and evaluate the clinical spectrum and disease severity of pediatric blepharokerato- conjunctivitis in Asian eyes. of the minimal angle of resolution units (P < .001) after appropriate medical and surgical intervention. CONCLUSIONS: Pediatric blepharokeratoconjunctivitis patients in Asia seem to have a more severe clinical presentation and course. Early and adequate management Accepted for publication Aug 25, 2011. From the Singapore Eye Research Institute, Singapore, Republic of Singapore (L.T., J.S.M., H.M.H., D.T.H.T.); the Singapore National Eye Centre, Singapore, Republic of Singapore (L.T., J.S.M., D.T.H.T.); the Office of Clinical Sciences, Centre for Quantitative Medicine, Duke- National University of Singapore Graduate Medical School, Singapore, Republic of Singapore (H.M.H.); the Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore (J.S.M., D.T.H.T.); and the Depart- ment of Clinical Sciences, Duke-National University of Singapore Graduate Medical School, Singapore, Republic of Singapore (J.S.M.). Inquiries to Donald T. H. Tan, Singapore National Eye Research Institute, 11 Third Hospital Avenue, Singapore 168751, Republic of Singapore; e-mail: snecdtpacific.net.sg METHODS THIS STUDY WAS A RETROSPECTIVE CASE SERIES. ALL PA- tients who were diagnosed with pediatric blepharokerato- conjunctivitis at a tertiary referral center in Singapore from 1991 through 2010 were included. Only patients 16 years of age and younger at presentation were included in the study. Blepharokeratoconjunctivitis was defined clini- cally as the presence of eyelid involvement by lid margin scarring, blepharitis, meibomitis, and chalazion or hordeo- lum, accompanied by epithelial or stromal keratitis, cor- neal scarring, vascularization, and thinning or perforation. The demographics, clinical presentation, and management outcomes of each patient were recorded. 564 © 2012 BY ELSEVIER INC. ALL RIGHTS RESERVED. 0002-9394/$36.00 doi:10.1016/j.ajo.2011.08.037 VOL. 153, NO. 3 PEDIATRIC BLEPHAROKERATOCONJUNCTIVITIS IN ASIAN EYES 565 35 68.6 13 25.5 12 23.5 11 21.6 7 13.7 5 9.8 4 7.8 3 5.9 2 3.9 1 2.0 1 2.0 Meibomitis Blepharitis Chalazion Stye Telangiectasia 44 86.3 39 76.5 23 45.1 12 23.5 1 2.0 Conjunctiva 34 66.7 Hyperemia 26 51.0 Papillae 17 33.3 Phlyctena 8 15.7 Follicles 6 11.8 Conjunctivitis 5 9.8 FIGURE 1. Pediatric blepharokeratoconjunctivitis in Asian eyes: clinical photographs of disease severity. (Left) Moderate disease showing corneal scar. (Right) Severe disease showing corneal scarring with thinning with the presence of a descemetocele in this case. The management protocol of our patients includes daily warm compress and lid hygiene, topical antibiot- ics, topical steroids, topical immunosuppressant, for example, cyclosporin A 0.5%, and systemic antibiotics and systemic steroids, depending on severity of the disease and response to treatment. Patients were graded based on documented clinical corneal findings at any point during the follow-up period. Those graded with mild disease had only corneal epithelial involvement without stromal scarring, for example, punctate epithelial erosions or superfi- cial punctate keratitis; moderate disease was defined as the additional presence of corneal stromal scarring, with or without vascularization; and severe disease was defined as corneal scarring with significant stromal thinning (Figure 1). Eye scrapings additionally were performed when an active infectious cause was suspected. Statistical significance was set at P .05. The chi- square and Fisher exact test were conducted for analyzing categorical data. The Wilcoxon signed rank test was conducted to compare paired preoperative and postopera- tive data. SPSS software version 17 (IBM Corporation, Armonk, New York, USA) was used for the analyses. Internal review board approval was secured for the study. TABLE 1. Pediatric Blepharokeratoconjunctivitis in Asian Eyes: Presenting Symptoms and Signs of Patients Symptoms and Signs Number Percentage Symptoms Redness Tearing Blurred vision Pain Irritation Photophobia White spot Swelling Discharge Itching Rubbing Signs Lid 51 100 RESULTS FIFTY-ONE PATIENTS WERE DIAGNOSED WITH PEDIATRIC blepharokeratoconjunctivitis at our center from 1991 through 2010. The mean age at presentation was 10.2 3.6 years. Females made up most of the patients: 41 (80.4%) of 51. The mean duration of follow-up was 58.9 44.0 months (range, 3 to 227 months). Most of the patient were Chinese (29/51; 56.9%), followed by Indian (13/51; 25.5%) and Malay (9/51; 17.6%). Bilateral disease was seen in most patients (33/51; 64.7%), unilateral disease in the right eye was seen in 27.5% (14/51) of patients, and unilateral disease in the left eye in was seen in 7.8% (4/51) of patients. The most Cornea 51 100 Corneal scar 47 92.2 Superficial vascularization 46 90.2 Punctate epithelial erosions or superficial punctate keratitis 38 74.5 Marginal infiltrates 26 50.9 Corneal phlyctena 19 37.3 Thinning 17 33.3 Deep vascularization 9 17.6 Limbitis 7 13.7 Perforation 2 3.9 common symptoms experienced were eye redness (35/51; 566 AMERICAN JOURNAL OF OPHTHALMOLOGY MARCH 2012 FIGURE 2. Pediatric blepharokeratoconjunctivitis in Asian eyes: case study of a patient with severe disease requiring tectonic lamellar keratoplasty. (Top left) Preoperative severe disease with progressive corneal thinning. Best-corrected visual acuity (BCVA): 6/24. (Top right) With optical slit to show degree of thinning. (Bottom left) Postoperative picture after deep lamellar keratoplasty. BCVA: 6/9. (Bottom right) Optical slit showing preservation of corneal integrity. 68.6%), tearing (13/51; 25.5%), and blurred vision (12/51, 23.5%; Table 1). All of the patients had lid and corneal changes, and 66.7% (34/51) had conjunctival changes. The most common lid pathologic features were meibomitis (44/51; 86.3%), blepharitis (39/51; 76.5%), and chalazion (23/51; 45.1%), whereas the most common corneal changes were corneal scarring (47/51; 92.2%), superficial vascularization (46/51; 90.2%), and punctate epithelial erosions or superficial punctate keratitis (38/51; 74.5%). Among the 51 patients, 56.9% (29/51) were graded as having moderate disease, 37.3% (19/51) were graded as having severe disease, and 5.9% (3/51) were graded as having mild disease. Eye cultures were performed in only 8 patients: 6 were corneal scrapings, 1 was a conjunctival swab, and 1 was an eyelid swab. One cornea specimen isolated Pseudomonas aeruginosa, and the conjunctival swab isolated Acinetobacter baumannii with coagulase-negative Staphylococcus. All other FIGURE 3. Pediatric blepharokeratoconjunctivitis in Asian eyes: image showing one of the patients with a spontaneous corneal perforation at presentation. The iris can be seen plugging the perforation site. culture results were negative. Four patients (7.9%) were diagnosed with a coexisting dermatologic condition: 3 of them were diagnosed with acne rosacea and 1 was diagnosed with acne vulgaris based on their cutaneous manifestations. All patients were treated with topical antibiotics, and the 3 most common topical antibiotics prescribed were fucidic acid gel (47/51; 92.2%), levofloxacin (26/51; 51.0%), and tobramycin eyedrops (22/51; 43.1%). All but 1 patient received treatment with topical steroids, and the 3 most commonly prescribed were dexamethasone 1% (45/51; 88.2%), prednisolone 0.12% to 1% (34/51; 66.7%), and fluorometholone 0.1% (19/51; 37.3%). The frequency of topical steroid treatment was tapered based on response to treatment, and the dosing regimen ranged from once every 2 hours to once every other day. The mean duration of topical steroids was 16.0 18.5 months. Topical cyclosporin A 0.5% was administered to 8 children (15.7%). Systemic antibiotic therapy was initiated in 19 patients (37.3%), and the older VOL. 153, NO. 3 PEDIATRIC BLEPHAROKERATOCONJUNCTIVITIS IN ASIAN EYES 567 TABLE 2. Pediatric Blepharokeratoconjunctivitis in Asian Eyes: Summary of Studies Conducted on Pediatric Blepharokeratoconjunctivitis No. of Age at Onset or Mean Follow-up Author, Year Country Patients Presentation (Range) Duration (Range) Ethnicity Gender (Ratio) Treatment Side Effects Farpour and McClellan,1 2001 Australia 8 Onset: 3.2 y (0.5 to 8 y); presentation: (3.5 to 13 y) 8.3 mos (2 to 23 mos) Not mentioned 5 F:3 M (1.67) Systemic: minor stomach disturbances (n 2), diarrhea (n 1); topical: None Viswalingam and associates,4 2005 United Kingdom 44 Onset: 4.1 y (1 to 14 y); presentation: 5.4 y (1 to 14 y) 7 y (7 mos to 12 y) 20 white, 22 Asian (Indian/Sri Lankan), 2 Middle Eastern 24 F:20 M (1.2) Not stated Hammersmith and associates,5 2005 USA 29 Onset: 4.1 y (0 to 8 y); presentation: 6.4 y (2 to 12 y) 5.4 mos (2 to 25 mos) 26 white, 1 Asian, 2 unknown 16 F:13 M (1.23) Systemic: gastrointestinal disturbances (n 2); topical: none Jones and associates,2 2007 United Kingdom 27 Onset: 4.5 y (5 mos to 13 y); presentation: 6.9 y (7 mos to 15.9 y) 2.3 y (5 mos to 6.1 y) 17 white, 8 Indian/ Pakistani, 1 Middle Eastern, 1 Chinese 14 F:13 M (1.08) Systemic: vaginal candidiasis; topical: punctate epithelial erosions from topical ciprofloxacin Doan and associates,6 2007 France 2 Onset: 7 3 y (1 mos to 13 y) 19 4 y Not mentioned 19 F:4 M (4.75) Not stated Gupta and associates,7 2010 Teo, 2011 (current study) India 615 Presentation: 6.7 y (7 mos to 16 y) Singapore 51 Presentation: 10.2 y (2 to 16 y) Not mentioned 58.9 mos (3 to 227 mos) Primarily Indian 29 Chinese, 13 Indian, 9 Malay 1 F:1.6 M (0.625) Not stated 41 F:10 M (4.1) Systemic: gastrointestinal disturbances (n 1); topical: raised IOP (n 7), cataract (n 1) F female; IOP intraocular pressure; M male; mos months; y year. children received oral doxycycline (16/19; 84.2%), whereas younger children younger than 9 years of age received erythromycin (3/19; 15.8%) or Augmentin (3/19; 15.8%) oral therapy. The mean duration of oral antibiotic adminis- tration was 1.9 4.2 months (range, 1 to 23 months). One patient had severe inflammatory disease that required sys- temic control with oral prednisolone. Five patients, all of whom were Chinese, required surgical intervention during their course of follow-up. Two patients underwent a deep lamellar keratoplasty for tec- tonic indications and 1 patient underwent the procedure for optical indications. The case study of a patient who underwent a deep lamellar keratoplasty is shown in Figure 2. Two other patients with spontaneous corneal perfora- tions (Figure 3) at presentation required cornea gluing, without graft surgery, with Histoacryl topical skin adhesive (B. Braun, Ann Arbor, Michigan, USA), a tissue sealant that consists of n-butyl-2 cyanoacrylate. Patients graded as having severe disease had a 26.3% chance of requiring subsequent surgical intervention for tectonic or optical indications as compared with patients who were graded as having moderate and mild disease (P .05, Fisher exact test (2 sided). Complications of treatment encountered in our study population include that of raised intraocular pressure in 7 (13.7%) patients, cataract in 1 (2%) patient, and gastrointestinal disturbance from oral antibiotics in 1 (2%) patient. Those with raised intraocular pressure were treated medically with good response, and in none of them did glaucoma develop during the course of their follow-up. At presentation, 17 eyes (33.3%) had poor vision (less than 0.3 logMAR). At final review, 8 (15.7%) of 51 eyes had persistently poor vision (P .01). Overall, the best-corrected visual acuity improved by 0.10 logMAR units (P .001,