녹내장 방수유출관삽입술의 안전성ㆍ유효성 평가

Abstract

평가배경 녹내장 방수유출관삽입술(Glaucoma Aqueous Tube Insertion)은 Ex-PRESSTM를 안구의 전방과 공막 사이에 삽입 이식하여 방수액을 배출시킴으로서 안압을 조절하는 기술로 2009년에 신의료기술평가를 받았다. 보건복지부는 비급여 항목 485개 의료기술을 모두 급여 항목으로 전환하기 위한 절차를 진행 중에 있으며, 동 기술은 2020년에 전환 예정인 항목 중 신의료기술평가를 받은 기술에 해당하여 이번 의료기술재평가 사업(NR19-001, 연구책임자: 최인순)의 일환으로 근거 업데이트를 수행하였다.

위원회 운영 총 5인으로 구성된 소위원회는 2019년 4월부터 2019년 7월까지 약 4개월간 총 3회의 소위원회 운영 및 1회 서면검토를 수행하였다.

평가 목적 및 방법 본 연구에서는 녹내장 방수유출관삽입술의 안전성 및 유효성을 재평가하기 위하여 기존 체계적 문헌고찰을 업데이트하는 방식으로 수행하였다. 신의료기술평가 당시 문헌검색 일자에 1년을 겹치도록 출판 연도를 제한하였으며, 결과적으로 2009년부터 검색일까지 발표된 문헌을 포함하였다. 동 기술에 대한 안전성 및 유효성 평가는 체계적 문헌고찰 방법론을 이용하고자 하며, 이와 관련한 세부 평가방법에 대해서는 “녹내장 방수유출관삽입술에 대한 안전성 및 유효성 평가 소위원회(이하 ‘소위원회’라 한다)”의 논의를 거쳐 확정하였다.

평가 결과 1. 문헌선정 결과 최종 선정된 문헌은 총 21편으로, 연구 설계별로 구분 시 실험연구로서 무작위배정비교임상연구가 11편, 관찰연구로 코호트연구가 10편이 포함되었다. 기 평가에 포함된 문헌 1편도 포함되었다. 2. 유효성 결과 유효성 지표로는 안압, 항녹내장약물수, 성공률, 실패율, 시력을 포함하였다. 무작위배정비교임상연구 중 Ex-PRESS군과 섬유주절제술군의 안압, 항녹내장약물수, 부분 성공률, 시력은 유의하지 않은 것으로 나타났다. 완전 성공률은 Ex-PRESS 군에서 더 높은 것으로 나타났다(RR 1.20, 95% CI 1.03,1.41) 코호트연구 중 Ex-PRESS군과 섬유주절제술군간에 유효성 지표에서 유의미하게 차이를 보인 결과 지표는 없었다.

3. 안전성 결과 유출관련 합병증으로는 얕은 전방, 편평전방, 수포유출, 맥락막박리, 맥락막삼출, 저안압성 황반변증, 저안압증 등을 포함하였다. 기구관련 합병증으로는 각막-기구 접촉, 총채-기구접촉, 튜브막힘, 기구이탈, 각막내피세포변화 등 을 포함하였다. 기타 합병증으로는 앞방출혈, 안압급등, 안구내염, 태논캡슐섬유화, 결막미란 등을 포함하였다. 무작위배정비교임상연구 중 Ex-PRESS군과 섬유주절제술군간에 유의미하게 차이를 보인 안전성 결과 지표는 각막내피세포변화, 앞방출혈, 전반적인 합병증이었다. 코호트연구 중 Ex-PRESS군과 섬유주절제술군간에 유의미하게 차이를 보인 안전성 결과 지표는 맥락막박리, 각막내피세포변화, 앞방출혈이었다.

4. 근거수준 평가결과 최종 선택된 문헌에 대해서 연구설계, 비뚤림 위험, 비일관성, 비정밀성, 기타 고려사항 등을 고려하여 결과변수 중요도가 ‘매우 중요함(critical)’과 ‘중요함(important but not critical)’으로 결정된 변수에 한하여 근거수준 평가를 수행하였다. 무작위배정비교임상연구, 코호트 연구 모두 결과변수 중 중요도가 ‘매우 중요함’인 결과변수 ‘안압’, ‘완전성공률’, ‘부분성공률’ 모두 ‘low’로 평가하였다. 중요도가 ‘중요함’인 결과변수 ‘각막내피세포변화’, ‘얕은 전방’, ‘편평전방’, ‘맥락막박리’, ‘저안압성 황반변증’, ‘앞방출혈’, ‘안구내염’ 모두 ‘low’로 평가되었다.

결론 녹내장 방수유출관삽입술 소위원회는 현재 평가 결과에 근거하여 다음과 같이 제언하였다. 소위원회는 녹내장 방수유출관삽입술은 약물사용에도 조절되지 않는 개방각녹내장, 가성탈락녹내장, 색소성녹내장 환자 등에서 섬유주절제술과 비교시 그 합병증이 유사하거나 낮은 수준이고, 안압 조절, 항녹내장 약물사용 감소 및 시력의 호전에 있어서도 효과가 유사한 수준이고, 완전 성공에 있어서는 효과가 있는 것으로 나타나 안전하고 유효한 기술로 평가하였다. 의료기술재평가위원회는 “녹내장 방수유출관삽입술”에 대해 소위원회 검토결과에 근거하여 다음과 같이 심의하였다(2019.12.13) 의료기술재평가위원회는 녹내장방수유출관삽입술은 약물사용에도 조절되지 않는 개방각녹내장, 가성탈락녹내장, 색소성녹내장 환자 등에서 섬유주절제술과 비교 시 그 합병증이 유사하거나 낮은 수준이고, 안압 조절, 항녹내장 약물사용 감소 및 시력의 호전에 있어서도 효과가 유사한 수준으로 나타나 안전하고 유효한 기술로 판단한 소위원회 결론은 타당하나, 본 평가결과 근거수준이 낮아 향후 추가적으로 검토가 필요하다고 심의하였다.

Background Glaucoma aqueous tube insertion is used to regulate intraocular pressure by inserting Ex-PRESSTM between the anterior chamber and sclera to drain aqueous humor. The technology underwent New Health Technology Assessment (nHTA) in 2009. The Korea Ministry of Health and Welfare is in the process of transitioning the coverage status of each of 485 health technologies currently not covered by the national health insurance to a benefit item. The technology is one of the items that was planned for coverage status change in 2020 and had previously undergone a New Health Technology Assessment research. As part of the Health Technology Reassessment Project (NR19-001, principal investigator: In Soon Choi), evidence regarding the technology was updated.

Subcommittee operation The 5-member Subcommittee made assessment on this procedure in accordance with the literary grounds through operation of the Subcommittee 3 times over a period of approximately 4 months from April and July 2019, and submitted the results of the review.

Purposes and Methods This study was conducted to update the outcomes of the using systematic review and reassess the safety and effectiveness of glaucoma aqueous tube insertion. The publication year was restricted such that the starting year would overlap by one year with the literature search performed for the New Health Technology Assessment research. Consequently, the literature published from 2009 to the date of literature search for this study were included. To assess the safety and effectiveness of the said technology, a systematic review was performed. Methods details were determined by the “Subcommittee for the Safety and Effectiveness Assessment of Glaucoma Aqueous Tube Insertion".

Results 1.Selected articles A total of 21 articles were finally selected. Grouped by study design, 11 articles were randomized controlled clinical trials (RCT) and 10 were cohort studies. One of the articles had been included in the New Health Technology Assessment research in 2009.

2.Effectiveness Effectiveness of Glaucoma Aqueous Tube Insertion as assessed by ocular pressure, the number of anti-glaucoma medications, (complete, partial) success rate, failure rate, and visual acuity on the basis of total of 21 literature. In the RCTs, ocular pressure, the number of anti-glaucoma medications, partial success rate, and visual acuity were not significantly different in the Ex-PRESS and trabeculectomy groups. The complete success rate was higher in the Ex-PRESS group (RR 1.20, 95% CI 1.03,1.41). In the cohort studies, the effectiveness outcomes of the Ex-PRESS and trabeculectomy groups were not significantly different.

3.Safety Safety of Glaucoma Aqueous Tube Insertion was assessed by categorizing safety issues into aqueous tube insertion related complications, apparatus related complications and other complications following the surgery on the basis of total of 10 literatures. Shallow anterior chamber, flat anterior chamber, bleb drainage, choroidal detachment, choroidal exudation, low-pressure macular degeneration, and low ocular pressure were evaluated as drainage-related complications. Cornea-device contact, iris-device contact, blocked tube, device dislocation, and change in corneal epithelial cells were evaluated as device-related complications. Other complications evaluated include hyphema, a rapid increase in ocular pressure, intraocular inflammation, Tenon's capsule fibrosis, and conjunctival erosion. In the RCTs, the Ex-PRESS and trabeculectomy groups showed significantly different changes in corneal epithelial cells, hyphema, and overall complications. In the cohort studies, the Ex-PRESS and trabeculectomy groups showed significant differences in choroidal detachment, changes in corneal epithelial cells, and hyphema.

4.Quality of the evidence The quality of the evidence was considered based on the study design, risk of bias, inconsistency, imprecision, and other considerations of the finally selected articles. The evidence quality grading was limited to those outcome variables for which the level of importance was "critical" or "important but not critical." In the RCTs and cohort studies, all outcome variables for which the level of importance was "critical" (namely, ocular pressure, complete success rate, partial success rate) were graded to be of "low" quality. In addition, all outcome variables for which the level of importance was "important but not critical" (namely, change in corneal epithelial cells, shallow anterior chamber, flat anterior chamber, choroidal detachment, low-pressure macular degeneration, hyphema, and intraocular inflammation) were graded to be of "low" quality as well.

Conclusion The Sub-committee made the following conclusions on “Glaucoma Aqueous Tube Insertion” on the basis of currently available literatures. In comparison to trabeculectomy, glaucoma aqueous tube insertion showed similar or fewer complications in patients with open-angle glaucoma, pseudoexfoliation glaucoma, and pigmentary glaucoma (types of glaucoma that cannot be controlled by medications). Additionally, glaucoma aqueous tube insertion showed similar effectiveness in regulating ocular pressure regulation, reducing the use of anti-glaucoma medications, and improving visual acuity; they also showed greater complete success rates. Accordingly, the subcommittee assessed that glaucoma aqueous tube insertion is safe and effective. Health Technology Reassessment Committee made the following deliberations on “Glaucoma Aqueous Tube Insertion” on the basis of the results of review by the Sub-committee (December 13, 2019). The Health Technology Reassessment Committee considered that the subcommittee's assessment is reasonable. They considered glaucoma aqueous tube insertion as safe and effective given that it had similar or fewer complications than trabeculectomy and was similarly effective in regulating ocular pressure, reducing the use of anti-glaucoma medications, and improving visual acuity in patients with open-angle glaucoma, pseudoexfoliation glaucoma, and pigmentary glaucoma (conditions not controlled with drug therapy). However, the quality of the evidence is low. Accordingly, the committee determined that an additional review would be necessary in the future.