CLINICAL SCIENCE

Corneal Tattooing and Anterior Stromal Puncture for Treating Symptomatic Bullous Keratopathy

Hsin-Chiung Lin, MD,*† Yi-Lun Wang, MD,† Guang-Wu Chen, PhD,‡ and Chieh-Hung Yen, MD*

5-year survival rate of grafts is approximately 73%, but Purpose: fi To investigate the ef cacy of corneal tattooing, through endothelial cell counts progressively decline over the first 10 anterior stromal puncture (ASP), for managing painful bullous years after surgery.1,2 For patients who are not expected to keratopathy (BK). gain vision after a corneal transplant, alternative, nonsurgical Methods: This retrospective, case-controlled, consecutive case interventions may be able to provide temporary pain relief. series study was performed at a university-based referral clinic. These procedures include therapeutic contact lens (TSCL) use and anterior stromal puncture (ASP). Patients with painful BK who underwent corneal tattooing with fi Chinese ink between 2007 and 2013 were included in analyses. The rst use of a corneal dates back to 1859, when the procedure was performed to repair pigmentary Patients diagnosed with symptomatic BK who only underwent ASP 3 during the same period were included as a control group. defects related to leucoma. However, the use of corneal tattooing has been limited because of advancements in Results: A total of 40 patients (27 men, 13 women) with a mean keratoplasty, TSCL fitting, and ocular prostheses.4–8 In age of 57.5 6 15.3 years were included in analyses. The clinical general, corneal tattooing is performed for cosmetic purposes diagnosis was pseudophakic BK in 5 subjects (12.5%), failed graft in on eyes that have a corneal scar.9–11 Here, we compare BK 11 subjects (27.5%), BK secondary to perforating corneal injury recurrence rates after ASP and corneal tattooing. repair in 19 subjects (47.5%), and end-stage glaucoma in 5 subjects (12.5%). Subjects were followed for a mean period of 26.4 6 7.5 months (range: 6–55 months). Recurrent bullae formation occurred MATERIALS AND METHODS in 3 of 31 patients (9.68%) who had undergone corneal tattooing and in all 9 patients (100%) who had undergone ASP (P , 0.001). This study protocol was approved by the Human Research Ethics Committee at Chang Gung Memorial Conclusions: Corneal tattooing with Chinese ink is a simple, Hospital in Taiwan (No. 103-3480B) and all study conduct effective outpatient procedure for treating painful BK in eyes with no adhered to the tenets of the Declaration of Helsinki. Patient visual potential. information obtained from medical records was deidentified before analyses. Key Words: , bullous keratopathy The medical records of patients with painful BK who (Cornea 2016;35:355–357) underwent ASP or corneal tattooing between 2007 and 2013 were examined. Painful BK was defined as corneal edema and bullae formation secondary to traumatic, inflammatory, or orneal edema resulting from endothelial decompensation iatrogenic damage. All patients had documented endothelial Cis a major cause of pain and decreased vision in patients cell dysfunction or had undergone at least 2 failed penetrating with bullous keratopathy (BK), which is manifested by keratoplasty (PK) procedures. Patients with neurotrophic stromal edema and small vesicle (bullae) formation. Corneal keratopathy, Stevens–Johnson syndrome, or chemical burns transplantation, where the nonfunctioning endothelium is that might impede corneal reepithelialization were excluded replaced, is most commonly used to treat BK. Successful from analyses. The presence of a systemic disease known to surgeries can restore vision and alleviate ocular pain. The delay corneal healing (eg, diabetes mellitus) was noted. Chinese ink in solid form was sterilized using ethylene oxide gas sterilization, after which it was diluted and ground with Received for publication August 19, 2015; revision received October 1, 2015; distilled water into liquid form and introduced into the corneal accepted October 4, 2015. Published online ahead of print November 25, stroma with a bent 25- or 27-gauge needle with the same 2015. method used to perform ASP in the control group (no Chinese From the *Department of Ophthalmology, Chang Gung Memorial Hospital, ink in needle). The actual number of corneal tattoos placed Taoyuan, Taiwan; †School of Medicine, Chang Gung University, Taoyuan, Taiwan; and ‡Department of Computer Science and Engineering, College with ASP varied in each patient according to the location and of Engineering, Chang Gung University, Taoyuan, Taiwan. area affected by bullae formation. All procedures were Supported by Chang Gung Memorial Hospital (No. CMRPG3C1781). performed in the outpatient setting on eyes with no hope The authors have no conflicts of interest to disclose. for vision improvement. After the procedures, patients were Reprints: Hsin-Chiung Lin, MD, Department of Ophthalmology, Chang Gung Memorial Hospital, #5, Fu-Hsing St, Kweishan, Taoyuan 333, instructed to wear a TSCL for temporary pain relief and to Taiwan (e-mail: [email protected]). promote reepithelialization. Patients were also instructed to Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. use topical 0.25% chloramphenicol or fluoroquinolone 4

Cornea  Volume 35, Number 3, March 2016 www.corneajrnl.com | 355

Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Lin et al Cornea  Volume 35, Number 3, March 2016

RESULTS TABLE 1. Patient Demographic and Ocular Characteristics A total of 40 consecutive patients [13 women (32.5%), Tattoo 6 ASP Group Group P 27 men (67.5%)] with a mean age of 57.5 15.3 years (range: 25–82 years) were included in analyses. The ASP group No. eyes 9 31 consisted of 9 patients and the corneal tattoo group consisted of Age (yrs) 53.9 6 15.4 58.5 6 15.4 31 patients. Four patients had diabetes and 3 patients had Sex (male/female) 7/2 20/11 hypertension. All patients had disfiguring corneal edema and System disease (diabetes/hypertension) 1/1 3/2 opacities that had resulted from traumatic or surgery-related Eye (right/left) 3/6 21/10 endothelial dysfunction. The assigned clinical diagnosis was Visual acuity pseudophakic/aphakic BK in 5 patients (12.5%), graft failure in Before procedure (NLP/LP/HM/CF) 8/0/0/1 24/3/3/1 11 patients (27.5%), postperforating corneal injury repair After procedure (NLP/LP/HM/CF) 8/1/0/0 24/3/3/1 edema/opacity in 19 patients (47.5%), and end-stage glaucoma Diagnoses* in 5 patients (12.5%). Patients were followed for an average Perforating injury 4 10 period of 26.4 6 7.5 months (range: 6–55 months). There were Ocular siderosis 1 0 no significant differences between the ASP and tattoo groups in Retinal detachment repair 2 1 patient age, sex, affected eye distribution (right, left), diabetes PK 3 14 or hypertension incidence, preoperative primary diagnosis, or Perforating 1 5 follow-up period duration (Table 1). Second glaucoma 7 14 The tattoo group consisted of 31 patients (20 men, 11 End-stage glaucoma 0 3 women) with a mean age of 58.5 6 15.4 years (range: 25–82 Chronic angle closure glaucoma 0 1 years). There was more severe ciliary congestion in the first Neovascular glaucoma 0 1 week after procedures in the tattoo group than in the control Pseudophakic BK 2 8 group. One month after undergoing corneal tattooing, 10 of Follow-up period (mo) 31.3 6 13.2 25.0 6 13.3 31 patients (32.6%) had complete epithelial bullae regression Bullae recurrence 9 (100%) 3 (9.7%) ,0.001 and most patients had at least partial regression of bullae. Treatment for recurrence Three months after tattooing, 28 of 31 patients (90.3%) were Corneal tattoo 5 1 symptom free and had no recurrence of bullae. Unfortunately, Conjunctival flap 2 1 3 patients (9.7%) had recurrent bullae formation and received Bandage contact lens 2 1 conjunctival flaps or a TSCL to relieve symptoms. Data presented as mean 6 standard deviation, where applicable. The ASP group (control group) consisted of 9 patients *Indicates that many patients also had glaucoma, which was the secondary (2 women, 7 men) with a mean age of 53.9 6 30.2 years diagnosis. – CF, counting fingers; HM, hand motion; LP, light perception; NLP, no light (range: 25 76 years). One patient had diabetes and 1 patient perception. had hypertension. All 9 patients (100%) had varying degrees of painful bullae recurrence by 3 months that required treatment with alternative procedures (eg, corneal tattooing times a day until the epithelium had healed. After healing, the or conjunctival flap creation). The difference between bullae TSCL was removed, chloramphenicol or fluoroquinolone use recurrence rates in the ASP (100%) and tattoo (7.5%) groups was discontinued, and Tobradex ointment use (twice a day was statistically significant (P , 0.001, Table 1). application; Alcon, Belgium) was initiated. Patients were examined at 1 day, 7 days, and 1 month after ASP or tattooing and every 3 months after that. Patient DISCUSSION symptoms, corneal findings, and visual acuity at the last Corneal tattooing has been used to improve the follow-up visit were noted. Procedural failure was defined as cosmetic appearance of eyes with corneal opacities and bullae recurrence 3 months or more after the procedure. defects for more than a century. Alio et al recently renamed A Fisher exact test was used to examine the difference the technique as “keratopigmentation” and used a new between groups in bullae recurrence. P-value examined was material, applied using a femtosecond laser, for both cosmetic 2-tailed and statistical significance was defined as P , 0.05. and optical function improvement.10,12–15

FIGURE 1. A, Ocular photograph of a 39-year-old man with sustained corneal perforating injury and BK with recurrence of pain. B, Corneal inflammation with ciliary congestion 1 week after treatment with corneal tattooing.

356 | www.corneajrnl.com Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Cornea  Volume 35, Number 3, March 2016 Corneal Tattoos and Bullous Keratopathy

This retrospective, consecutive case series investigated conjunctival flap and TSCL) do not offer. Therefore, we the efficacy of corneal tattooing through ASP in eyes with no suggest that corneal tattooing should be considered for visual potential but that had persistent painful bullous corneal treating painful recurrent BK, particularly in eyes with erosion. Kim et al16 reported good success rates for treating a disfigured appearance. Success with this minimally invasive BK with corneal tattooing in conjunction with amniotic procedure could prevent some patients from needing more membrane transplantation. We speculate that the presence aggressive surgery. of a foreign body (in this case, the ) in the cornea induces higher levels of inflammation, promoting epithelial REFERENCES adhesion. 1. Ing JJ, Ing HH, Nelson LR, et al. Ten-year postoperative results of Several treatments have been proposed for eyes with penetrating keratoplasty. Ophthalmology. 1998;105:1855–1865. symptomatic BK that will likely not gain vision with PK. 2. Patel SV, Hodge DO, Bourne WM. Corneal endothelium and post- operative outcomes 15 years after penetrating keratoplasty. Trans Am These treatments have had varying levels of success in Ophthalmol Soc. 2004;102:57–65. alleviating patient pain and include topical hypertonic 3. Leigh A. Tattooing of the Cornea. St. Louis, MO: Mosby; 1965. solution application, TSCL use, anterior stromal cauteriza- 4. Beekhuis WH, Drost BH, van der Velden/Samderubun EM. A new tion, ASP, excimer laser phototherapeutic keratectomy, treatment for photophobia in posttraumatic : a case report. – amniotic membrane transplantation, and conjunctival flap Cornea. 1998;17:338 341. 17–21 5. Remky A, Redbrake C, Wenzel M. Intrastromal corneal tattooing for iris creation. Sridhar et al successfully achieved symptomatic defects. J Refract Surg. 1998;24:1285–1287. relief with ASP in 28 patients with BK. Ten patients (35.7%) 6. Burris TE, Holmes-Higgin DK, Silvestrini TA. Lamellar intrastromal had complete regression of epithelial bullae and the remaining corneal tattoo for treating iris defects (artificial iris). Cornea. 1998;17: 18 patients (62.3%) had partial regression of bullae. Histo- 169–173. 7. Dawson E, Maino A, Lee J. A unique use for a corneal tattoo. logical examination of corneal buttons after PK procedures Strabismus. 2009;17:98–100. showed that subepithelial fibrosis, vascularization, and 8. Anastas CN, McGhee CN, Webber SK, et al. Corneal tattooing revisited: inflammation had occurred. Therefore, they concluded that excimer laser in the treatment of unsightly leucomata. Aust N Z J ASP might prevent BK recurrence by enhancing adhesion by Ophthalmol. 1995;23:227–230. a scarring process.22 We observed a higher recurrence rate in 9. Alio JL, Sirerol B, Walewska-Szafran A, et al. Corneal tattooing (keratopigmentation) with new mineral micronised pigments to restore our ASP group than that observed by Sridhar et al, which we cosmetic appearance in severely impaired eyes. Br J Ophthalmol. 2010; attribute, in part, to differences in preprocedural diagnoses. In 94:245–249. our study, 5 patients (55.6%) in the ASP group had 10. Chang KC, Kwon JW, Han YK, et al. The epidemiology of cosmetic a perforating injury that resulted in anterior segment destruc- treatments for corneal opacities in a Korean population. Korean J Ophthalmol. 2010;24:148–154. tion, uncontrollable intraocular pressure, and vision loss. In 11. Lee JE, Jun JB, Choi HY, et al. Corneal tattooing to mask subsequent the study by Sridhar et al, more than 90% of included patients opacification after amniotic membrane grafting for stromal corneal ulcer. had pseudophakic/aphakic BK or Fuchs dystrophy. However, Acta Ophthalmol Scand. 2006;84:696–698. in our study, none of the ASP patients had Fuchs dystrophy 12. Alió JL, Rodriguez AE, Toffaha BT, et al. Femtosecond-assisted and only 1 patient (11.1%) had pseudophakic/aphakic BK. keratopigmentation for functional and cosmetic restoration in essential iris atrophy. J Cataract Refract Surg. 2011;37:1744–1747. There were also ASP procedural differences because our 13. Alio JL, Rodriguez AE, Toffaha BT, et al. Femtosecond-assisted patients received fewer than 200 punctures. keratopigmentation double tunnel technique in the management of a case Our study results showed a significantly lower BK of Urrets-syndrome. Cornea. 2012;31:1071–1074. recurrence rate in eyes that underwent corneal tattooing 14. Alio JL, Rodriguez AE, Toffaha BT. Keratopigmentation (corneal tattooing) for the management of visual disabilities of the eye related (9.7%) than in eyes that underwent ASP (100%). As already to iris defects. Br J Ophthalmol. 2011;95:1397–1401. stated, we believe that the Chinese ink resulted in a more 15. Amesty MA, Alio JL, Rodriguez AE. Corneal tolerance to severe inflammatory reaction than ASP alone. This would micronised mineral pigments for keratopigmentation. Br J Ophthalmol. have induced more severe ciliary congestion after the corneal 2014;98:1756–1760. tattooing procedure (Fig. 1), which would have promoted 16. Kim YK, Han YK, Wee WR, et al. 7 cases of combined corneal tattooing – and amniotic membrane transplantation in bullous keratopathy. J Korean epithelial stromal adhesion during the wound-healing pro- Ophthalmol Soc. 2008;49:503–508. cess. It took 1 to 3 months for the irregular corneal surface to 17. Gomes JA, Haraguchi DK, Zambrano DU, et al. Anterior stromal smooth out after corneal tattooing. Because of the relatively puncture in the treatment of bullous keratopathy: six-month follow-up. long healing and TSCL-wearing period after ASP, patients Cornea. 2001;20:570–572. 18. Gregory ME, Spiteri-Cornish K, Hegarty B, et al. Combined amniotic should be educated on the signs and symptoms of cornea membrane transplant and anterior stromal puncture in painful bullous infection. As a prophylactic measure, patients included in this keratopathy: clinical outcome and confocal microscopy. Can J Oph- study were instructed to use topical antibiotics and attend thalmol. 2011;46:169–174. regular follow-up appointments. No TSCL-related keratitis 19. Paris Fdos S, Goncalves ED, Campos MS, et al. Amniotic membrane was observed in our study population. transplantation versus anterior stromal puncture in bullous keratopathy: a comparative study. Br J Ophthalmol. 2013;97:980–984. This study was limited by its retrospective nature and 20. Tsai TC, Su CY, Lin CP. Anterior stromal puncture for bullous relatively small sample size. Larger clinical studies on the use keratopathy. Ophthalmic Surg Lasers Imaging. 2003;34:371–374. of corneal tattooing are needed. Additionally, histological 21. Lin PY, Wu CC, Lee SM. Combined phototherapeutic keratectomy and and/or animal studies are needed to better understand the therapeutic contact lens for recurrent erosions in bullous keratopathy. Br J Ophthalmol. 2001;85:908–911. effect of Chinese ink on corneal wound healing. In addition to 22. Sridhar MS, Vemuganti GK, Bansal AK, et al. Anterior stromal puncture relieving pain, the tattooing procedure also improved patient in bullous keratopathy: a clinicopathologic study. Cornea. 2001;20: appearance, a benefit that other alternative procedures (eg, 573–579.

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. www.corneajrnl.com | 357

Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.