Prosthetic Replacement of the Ocular Surface Ecosystem Scleral Lens Therapy for Patients With Ocular Symptoms of Chronic Stevens-Johnson Syndrome MARTIN HEUR, DIANNE BACH, CHRISTOS THEOPHANOUS, AND GLORIA B. CHIU PURPOSE:
To evaluate the results of Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) scleral lens treatment on visual acuity and function in patients with ocular symptoms of chronic StevensJohnson syndrome (SJS). DESIGN: Retrospective interventional case series. METHODS: SETTING: Single multi-specialty institutional practice. STUDY POPULATION: A chart review from July 2009 to July 2013 identified 19 patients with ocular symptoms from chronic SJS who were referred for PROSE fitting evaluation. Three patients deemed appropriate candidates were excluded because they were lost to follow-up during the fitting process. Only 1 eye was fitted in 4 patients because anatomic changes prohibited PROSE fitting in the fellow eye. Another patient chose to have PROSE fitting only in 1 eye. A total of 27 eyes of 16 patients who completed PROSE fitting were included in this study. INTERVENTION: PROSE scleral lens fitting. OUTCOME MEASURES: Visual acuity and visual function were assessed before and after PROSE fitting using Snellen acuity and Ocular Surface Disease Index (OSDI) survey. The OSDI survey is a validated questionnaire that assesses ocular surface disease in the context of vision-related function, ocular symptoms, and environmental triggers. RESULTS: Visual acuity improved from 0.43 ± 0.35 logMAR pre-PROSE to 0.14 ± 0.22 logMAR postPROSE (P [ .0007) in SJS patients. OSDI scores improved from 70.4 ± 19.0 pre-PROSE to 37.4 ± 23.2 post-PROSE (P [ .0002) in the same cohort. CONCLUSION: The results of this study show that PROSE treatment is a viable option for improving visual acuity and function in SJS patients who failed conventional treatment. (Am J Ophthalmol 2014;-:-–-. Ó 2014 by Elsevier Inc. All rights reserved.)
TEVENS-JOHNSON SYNDROME (SJS) AND THE MORE
severe toxic epidermal necrolysis (TEN) are forms of hypersensitivity reactions that lead to blistering of skin and mucous membranes. Ocular involvement from Accepted for publication Mar 20, 2014. From the Department of Ophthalmology, Keck School of Medicine of University of Southern California, Los Angeles, California. Inquiries to Martin Heur, Department of Ophthalmology, Keck School of Medicine of University of Southern California, 1450 San Pablo St, DEI 5702, Los Angeles, CA 90033; e-mail: [email protected]
SJS and TEN leads to cicatrization of the ocular surface, which results in pain and impaired vision that can be debilitating and frustrating for the patient.1–3 In the acute phase of SJS, ocular manifestations can range from a mild conjunctivitis to sloughing of large areas of conjunctiva. Management of the initial phase is geared toward controlling ocular surface inflammation that can rapidly progress to conjunctival sloughing. This can be accomplished using a variety to medical therapies, such as topical corticosteroids, and surgical procedures, including amniotic membrane transplantation.4–8 The use of systemic corticosteroids in SJS remains controversial. Although early recognition and intervention can minimize the ocular sequelae of chronic SJS, a majority of patients experience some degree of ocular surface cicatrization and a significant portion of these patients suffer debilitating consequences. Signs of ocular surface cicatrization can range from mild subconjunctival fibrosis to symblepharon formation and forniceal foreshortening with conjunctivalization of the corneal surface. Patients can experience foreign body sensation and pain from these changes, and those with changes to the cornea can also experience vision loss attributable to compromised corneal transparency. Chronic ocular changes also lead to limbal stem cell deficiency, making patients with vision loss from corneal changes poor candidates for corneal transplantation. Permanent keratoprosthesis is a feasible option for patients with severe vision loss, but long-term postoperative morbidity has tempered the initial enthusiasm for implantation of permanent keratoprosthesis. Examples of postoperative morbidity in SJS patients include sterile inflammation, carrier tissue melt leading to aqueous leak, skin retraction, formation of retroprosthetic membranes, and vision loss attributable to glaucoma.9 The outcome of keratoprosthesis implantation in SJS patients was noted to be substantially inferior to those in nonautoimmune conditions in the previously cited study. Fortunately for many patients with chronic ocular manifestations of SJS, conventional treatments, such as artificial tears, soft contact lenses, and oral supplements, can provide sufficient improvements in visual acuity and function. There is, however, a subgroup of patients who do not get satisfactory relief from conventional treatments. Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) treatment (Boston Foundation for Sight, Needham, Massachusetts, USA), uses a custom-designed scleral device that vaults the entire cornea and limbus and bathes
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it in a pool of nonpreserved sterile saline. The PROSE fitting process involves the use of a proprietary software program that allows for a highly customizable device that precisely fits the curvature of each patient’s eye to maximize vision and comfort.10 We hypothesized that PROSE scleral lenses would offer improvements in visual acuity and function for patients with chronic ocular manifestations of SJS who had failed conventional treatments. Several studies have previously shown that PROSE scleral lenses significantly improve visual acuity and functioning for patients with various ocular surface diseases.11–19 Prior to our study, the benefits of PROSE scleral lens therapy in SJS patients were evaluated in a limited number of studies, with outcomes based on visual acuity and clinical examination changes.13–15 The purpose of this study was to evaluate the results of our experience using PROSE scleral lenses for management of patients with ocular symptoms of chronic SJS who had failed conventional treatments, with outcomes based on visual acuity and function. To our knowledge, this study represents the largest group of SJS patients fitted with PROSE scleral lenses using visual function as an outcomes measure.
was obtained at completion of the lens fitting. Visual acuities were then converted from Snellen acuity to logarithm of the minimal angle of resolution (logMAR) acuity for statistical analysis.20 Visual function was assessed before and after PROSE fitting using the Ocular Surface Disease Index (OSDI), a validated 12-item questionnaire designed to grade severity of ocular surface disease in the context of vision-related function, ocular symptoms, and environmental triggers.21 Each item is scored on a scale of 0–4, and the final score is calculated by summing the individual scores of all questions answered 3 100 divided by the total number of questions answered 3 4. Pre-PROSE OSDI scores were obtained from the patient at the initial consultation visit, and postPROSE OSDI scores were obtained at least 6 months after the last fitting visit via telephone by a trained interviewer masked to the patient’s clinical information. Fourteen of 16 total patients, 11 of 11 male and 3 of 5 female patients, completed the post-PROSE OSDI interview. One female patient could not be reached after moving out of the country and the other declined to participate for unspecified reasons. For statistical analysis, all data sets were assumed to have a normal distribution. Thus, homoscedastic 2-tailed t tests were conducted to compare pre- and post-PROSE VA and OSDI scores using the statistical package in Excel 14.3.8, Microsoft, Redmond, Washington.
THE UNIVERSITY OF SOUTHERN CALIFORNIA (USC) INSTI-
tutional Review Board retrospectively approved this retrospective interventional case series study at a single multi-specialty institutional practice. Visual acuity and visual function data were collected from charts of patients who consented for the use of their clinical data per Health Insurance Portability and Accountability Act guidelines. A chart review of SJS patients with chronic ocular manifestations who had failed conventional treatments and were referred to the USC Eye Institute for PROSE fitting evaluation between July 1, 2009 and July 30, 2013 identified 19 patients. Three patients deemed appropriate candidates were excluded because they were lost to follow-up during the fitting process. Only 1 eye was fitted in 5 patients because 1 patient was status post-enucleation in the fellow eye, 1 patient chose not to proceed in the fellow eye owing to unsatisfactory vision improvement, 2 patients had clinical findings in their fellow eye (1 with extensive symblepharon and forniceal foreshortening and the other with permanent tarsorrhaphy) that made PROSE insertion prohibitively difficult, and 1 patient had minimal symptoms and chose not to proceed in the fellow eye. In total, data from 27 eyes of 16 patients were analyzed in this study. Visual acuity (VA) was obtained before and after PROSE treatment using a Snellen chart under standardized illumination with the projected image calibrated for the length of the examination room. Pre-PROSE VA was obtained using either manifest refraction or the patient’s device at the time of initial evaluation. Post-PROSE VA 2
RESULTS DATA FROM 27 EYES FROM 16 INDIVIDUALS WITH CHRONIC
ocular manifestations of SJS who completed PROSE treatment were analyzed in this retrospective study. There were 18 eyes of 11 male and 9 eyes of 5 female patients in our cohort, with a mean age of 40.3 6 11.2 years at the time of PROSE fitting. Female patients were slightly younger than male patients, 37.8 6 11.9 years vs 41.5 6 11.3 years, at the time of PROSE fitting, but their ages were not significantly different (P ¼ .56). Ocular features of our patients with chronic manifestations of SJS included keratinization of the lid margins, subconjunctival fibrosis, symblepharon, and conjunctivalization of the corneal surface (Figure 1). The PROSE device vaults the entire cornea and limbus and rests on the adjacent conjunctiva (Figure 1). The mean pre-PROSE VA of our SJS cohort was 0.43 6 0.35 logMAR (Figure 2). Male patients had a mean prePROSE VA of 0.47 6 0.39 logMAR while female patients had a mean pre-PROSE VA of 0.35 6 0.26 logMAR. There was no significant difference in pre-PROSE VA between male and female patients (P ¼ .41). The mean postPROSE VA in our SJS cohort was 0.14 6 0.22 logMAR, which represented a significant improvement over the prePROSE VA (P ¼ .0007). Male patients had a mean postPROSE VA of 0.15 6 0.25 logMAR and female patients had a mean post-PROSE VA of 0.13 6 0.13 logMAR.
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which represented a significant improvement (P ¼ .0002). Male patients had a mean post-PROSE OSDI score of 32.9 6 22.2, and female patients had a score of 53.8 6 22.4, indicating that there was no significant difference in postPROSE OSDI scores between male and female patients (P ¼ .17). Male patients showed a significant improvement in OSDI scores before and after PROSE treatment (P ¼ .0008), while female patients did not show a statistically significant difference (P ¼ .19). In our cohort, 11 of 11 male patients and 3 of 5 female patients completed the postPROSE OSDI interview. During the post-PROSE OSDI interview, patients were also asked whether they wore their PROSE devices all (100%), most (w75%), half (w50%), some (w25%), or none (stopped PROSE wear) of their waking hours. Seven of 14 of the patients reported wearing their PROSE devices all of the time and 5 of 14 patients reported most of the time, while only 2 patients reported none of the time during the post-PROSE OSDI interview. One patient reported a change in lens fit that caused introduction of air underneath the device, and another patient reported sufficient improvement in symptoms making further PROSE wear unnecessary.
DISCUSSION THIS RETROSPECTIVE CHART REVIEW STUDY DEMONSTRATED
FIGURE 1. Slit-lamp photograph of patient with ocular manifestations of chronic Stevens-Johnson syndrome. (Top) The keratinized eyelid margins, subconjunctival fibrosis, symblepharon, and conjunctivalized corneal surface are present. (Bottom) The Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) scleral lens vaults and bathes the entire cornea and limbus in nonpreserved saline. The black ink dot helps to distinguish orientation of the lens on the eye, and is also used to help the patient or the caregiver distinguish right and left lenses.
While there was no significant difference in post-PROSE VA between male and female patients (P ¼ .77), each group showed significant improvements in VA following PROSE fitting (P ¼ .006 for male patients and P ¼ .03 for female patients). In terms of Snellen acuities, the cohort improved from approximately 20/54 before to 20/28 after PROSE treatment. Of the 16 patients in the study, 14 completed the postPROSE OSDI survey. The mean pre-PROSE OSDI score of our SJS cohort was 70.4 6 19.0 (Figure 3). Male patients had a pre-PROSE OSDI score of 70.6 6 22.5, while female patients had a score of 70.0 6 9.2, indicating that there was no significant difference in pre-PROSE OSDI scores between male and female patients (P ¼ .96). The mean post-PROSE OSDI score of our SJS cohort was 37.4 6 23.2, VOL. -, NO. -
that PROSE scleral lens treatment significantly improved visual acuity and function in patients with chronic ocular manifestations of Stevens-Johnson syndrome (SJS). There were no differences in ages between male and female patients in our cohort. The visual acuity of the group improved significantly (P ¼ .0007) from before and after PROSE treatment. The statistical significance remained among male (P ¼ .006) and female (P ¼ .03) patient subgroups. The mean bestcorrected pre-PROSE visual acuity in our cohort was 0.43 logMAR with a range of 0.00–1.30 logMAR or Snellen acuity range of 20/20–20/400, indicating that there were several patients who had excellent vision prior to PROSE fitting. The mean best-corrected post-PROSE visual acuity in our cohort was 0.22 logMAR with a range of 0.00–1.00 logMAR or Snellen acuity range of 20/20–20/200. There were no differences in VA between male and female patients pre-PROSE (P ¼ .41) or post-PROSE (P ¼ .77), suggesting that there were no sex differences in VA in our cohort. Our study was not powered sufficiently to draw any conclusions regarding sex-based differences. Our findings were consistent with previous reports showing improvements in visual acuity following PROSE lens fitting in SJS patients with ocular manifestations.14,15 Our results also showed that the PROSE device was able to achieve significant improvements in our cohort, which included many patients who had very little room for VA improvement, underlying its effectiveness of enhancing VA in SJS patients with chronic ocular manifestations.
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FIGURE 2. Visual acuities pre (-) and post (,) Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) scleral lens therapy, represented as logarithm of the minimal angle of resolution (logMAR) in patients with ocular manifestations of chronic Stevens-Johnson syndrome. The mean visual acuity (VA) of the entire cohort improved from 0.43 ± 0.35 logMAR pre-PROSE to 0.14 ± 0.22 logMAR post-PROSE (*P [ .0007). Male patients improved from 0.47 ± 0.39 logMAR pre-PROSE to 0.15 ± 0.25 logMAR post-PROSE (#P [ .006). Female patients improved from 0.35 ± 0.26 logMAR pre-PROSE to 0.13 ± 0.13 logMAR post-PROSE (##P [ .03). There were no significant differences between male and female patients in either their pre-PROSE VA (P [ .41) or their post-PROSE VA (P [ .77).
FIGURE 3. Ocular Surface Disease Index (OSDI) scores pre (-) and post (,) Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) scleral lens therapy in patients with ocular manifestations of chronic Stevens-Johnson syndrome. The mean OSDI score of the entire cohort improved from 70.4 ± 19.0 pre-PROSE to 37.4 ± 23.2 post-PROSE (*P [ .0002). Male patients improved from 70.6 ± 22.5 prePROSE to 22.5 ± 22.2 post-PROSE (#P [ .0008). Female patients improved from 70.0 ± 9.2 pre-PROSE to 53.8 ± 22.4 post-PROSE (P [ .19). There were no significant differences between male and female patients in either their pre-PROSE OSDI scores (P [ .96) or their post-PROSE OSDI scores (P [ .17).
The mean pre-PROSE OSDI score for the entire group was 70.4 6 19.0, indicating significant impairment in patients’ daily activities. No differences in pre-PROSE OSDI scores between male (70.6 6 22.5) and female 4
(70.0 6 9.2) patients (P ¼ .96) indicated that there were no sex differences in functional impairment in our cohort. The mean post-PROSE OSDI score of the cohort was 37.4 6 23.2 (P ¼ .0002), demonstrating a significant functional improvement following PROSE fitting. This is consistent with a previous report anecdotally describing symptomatic relief in SJS patients following PROSE wear.14 There also were no differences in post-PROSE OSDI scores between male (32.9 6 22.2) and female (53.8 6 22.4) patients (P ¼ .17), suggesting that there were no sex differences in functional improvement following PROSE fitting. As with visual acuity, the small sample size precluded any conclusions regarding sex-based differences in OSDI scores. The fact that male but not female patients achieved statistical significance between pre- and post-PROSE OSDI scores likely reflects the sample size difference between the 2 groups, especially in the number of patients completing the post-PROSE OSDI interview (11 male vs 3 female). Nonetheless, the entire cohort showed a significant improvement between pre- and post-OSDI scores, indicating that our patients experienced improvements in ocular surface comfort and visual function. One of the strengths of this study was incorporating visual function in the outcomes analysis. The use of the OSDI survey provides a valid and reliable method to quantitatively measure improvements following PROSE treatment in the context of overall ocular symptoms, vision-related function, and environmental triggers. Our findings demonstrate the value of using visual function and quality, in addition to visual acuity, as an outcomes measure of PROSE scleral lens therapy in patients with chronic ocular manifestations of SJS. The post-PROSE OSDI surveys were conducted with the interviewer masked to patient symptoms, and provided an objective assessment of visual functioning before and after the lens was fitted. An interesting finding from this study was the relatively high PROSE acceptance rate among SJS patients. A total of 27 from a possible 37 eyes were fitted with PROSE devices. Eight eyes of 5 patients were excluded because they either chose not to proceed with the fitting or were lost to follow-up. It is unclear as to why 3 patients who were appropriate candidates were lost to follow-up. There were only 2 eyes of 2 patients in the cohort that were deemed to be poor candidates for clinical reasons; 1 had extensive symblepharon and forniceal foreshortening and the other had a permanent tarsorrhaphy, making PROSE insertion prohibitively difficult. A critical requirement for PROSE scleral lens fitting is that patients have grossly normal ocular surface anatomy (eg, extensive symblepharon, forniceal foreshortening, or the presence of a trabeculectomy bleb or tube shunt can make the fitting process prohibitive). The lens wear rate was also very high among this cohort, with 12 of 14 patients who completed the post-OSDI interview reporting consistent PROSE use of at least 75% of waking hours. These characteristics reflect an intrinsic ascertainment bias toward better post-PROSE VA and function because patients with extensive structural changes who
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may not have experienced improvements regardless of therapy or those who did not experience immediate improvement during the initial evaluation were excluded from the analysis. Another limitation of this study is the relatively small number of patients who were included. As our experience with PROSE scleral lens therapy grows, we anticipate changes in absolute values of VA and OSDI scores as we accumulate more SJS patients who are fitted with PROSE devices, but the significance and trends are not expected to change. Although this study did not have a control group to compare visual acuity, functioning, and quality among patients who did and did not receive the device, each subject served as his or her own internal control. A significant shortcoming of PROSE therapy is that it requires a highly motivated patient, as PROSE lens use is much more labor intensive compared to traditional contact lenses. Patients can feel intimidated and frustrated during training by the size of the lens and the amount of work needed for insertion, removal, and maintenance of PROSE lenses. Fortunately, patients with vision loss and pain secondary to ocular manifestations of chronic SJS tend to be very passionate about regaining functional vision and pain relief. It remains to be seen whether patients who have been fitted with PROSE scleral lenses can maintain
their motivation indefinitely. Aside from specialized contact lenses, other available therapies for patients with ocular signs and symptoms of chronic SJS include topical lubrication and autologous serum tears, conjunctival reconstruction, limbal stem cell transplantation, and keratoprosthesis. Although there have been reports of encouraging results,9,22–24 all of the currently available management strategies have inherent limitations and morbidities. In the future, the next big innovation in the management of these patients will likely come from the use of stem or pluripotent cell–derived tissues for anterior segment reconstruction, but long-term safety concerns such as potential tumorigenesis remain to be satisfactorily addressed. The best management of patients with chronic ocular manifestations of SJS currently still remains early recognition and aggressive treatment of the acute phase to minimize the chronic sequelae. Managing the ocular symptoms of chronic StevenJohnson syndrome can be difficult and frustrating. Although highly labor intensive, PROSE therapy can offer improvements in both visual acuity and function, even for those patients with very good acuity, without assuming the risks and the inevitable morbidity of surgery, and it should be considered in SJS patients with ocular symptoms.
ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST. M.H. receives research support from National Eye Institute (grant number EY021485) and Research to Prevent Blindness through grants to the University of Southern California for projects unrelated to this study. M.H. has served as paid expert reviewer for legal cases unrelated to this study. G.B.C. receives support from Allergan for work unrelated to this study. The other authors declare no conflicts of interest. This study was supported by a grant from Research to Prevent Blindness to the Department of Ophthalmology at Keck School of Medicine of University of Southern California. Contributions of authors: design of study (M.H., G.B.C.), conduct of study (M.H., G.B.C.), data collection and analysis (M.H., D.B., C.T., G.B.C.), manuscript preparation (M.H.), manuscript review and approval (M.H., D.B., C.T., G.B.C.).
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