及早治療眼高壓可以減少青光眼風險
作者：Laurie Barclay, MD
出處：WebMD醫學新聞
March 16, 2010 — 根據發表於3月眼科醫學誌(Archives of Ophthalmology)的隨機控制試驗結果，及早治療眼高壓可以降低發生青光眼的風險。
華盛頓大學醫學院Michael A. Kass醫師與「Ocular Hypertension Treatment Study (OHTS) Group」研究小組成員寫道，眼內壓(IOP)升高(眼高壓[OHT])是發生原發性廣角青光眼(primary open angle glaucoma，POAG)的主要風險因素，也是目前唯一可調整的風險因素。估計美國40歲以上者約4%-7%有OHT，對於這群發生青光眼風險高的人該如何處置一直有所爭論。
本研究的目標是比較早期和晚期治療對於降低POAG風險的安全性與效果，研究對象是1,636名眼高壓病患，開始時的IOP範圍是其中一眼24-32 mm Hg，另一眼21-32 mm Hg 。這些研究對象被隨機指派為接受觀察或者接受外用降眼壓藥物，藥物組中，治療期間中位數為13.0年，觀察組未予治療之期間中位數為7.5年，之後接受藥物治療之期間中位數為5.5年。
為了評估延遲治療是否與任何傷害有關，研究者比較了追蹤中位數13年時，原本觀察組以及原本藥物組後續發生POAG的累積病患比率。
整體而言，原本觀察組之此一比率為0.22(95%信心區間[CI]為0.19 - 0.25)、原本藥物組則是0.16 (95% CI，0.13 - 0.19) (P = . 009)，換言之，早期治療與降低27%的青光眼風險有關。至於開始時發生POAG風險最高的前三分之一患者，根據年紀、角膜厚度、開始時的IOP，兩組後來發生POAG的累積比率分別是0.40 (95% CI，0.33 - 0.46) 和0.28 (95% CI，0.22 - 0.34)。
研究作者寫道，與藥物相關之副作用增加的證據有限，開始時發生POAG風險最高的研究對象降低的絕對值最大，發生POAG風險最高者可以從較頻繁的檢查和早期預防治療中獲益。
OHTS研究的限制包括，選定的IOP降低目標為開始時的20%、不是流行病學研究之設計、診斷POAG的閾值相當高、使用便利抽樣樣本和人口基礎樣本比較。
研究作者寫道，我們相信個別化評估發生POAG風險將有助於病患和醫師決定檢查頻率，也有助於給予預防治療，醫師需考量病患的年紀、健康狀態、預期壽命、決定決策時的個人偏好等，最後，需要更久的追蹤，以確定隨機分組之下，延遲治療之傷害的程度，視力不佳的發生率與程度。
馬里蘭州巴爾的摩約翰霍普金斯大學Bloomberg公共衛生學院Alfred Sommer醫師在編輯評論中指出，醫師需考量治療IOP病患所造成的傷害是否大於好處。
Sommer醫師寫道，最後，醫師們受限於長久以來的一個問題：哪些人要治療、哪些人須觀察。Kass醫師等人這篇引人注目的文獻對於許多重要議題提供了有趣的觀點，但是沒有足夠資訊來引導我們。有許多高風險因素的年輕病患應接受預防治療、風險因素較少的年長病患則不需要，這些或許仍然有理，但有關眼高壓病患的最佳處置為何的無止盡討論和爭辯或許仍會繼續而不減少。
國家眼科研究中心以及國立少數民族健康與健康歧異中心、國家健康研究中心；Merck研究實驗室；Pfizer公司；以及防盲研究等支持本研究。研究作者與 Sommer醫師皆宣告沒有相關財務關係。
Early Treatment of Ocular Hypertension May Reduce Risk for Glaucoma
By Laurie Barclay, MD
Medscape Medical News
March 16, 2010 — Early treatment of ocular hypertension appears to reduce the risk for the development of glaucoma, especially in individuals at the highest risk, according to the results of a randomized controlled trial reported in the March issue of Archives of Ophthalmology.
"Elevated intraocular pressure (IOP) (ocular hypertension [OHT]) is a leading risk factor for the development of primary open angle glaucoma (POAG) and the only modifiable risk factor at present," write Michael A. Kass, MD, from Washington University School of Medicine in St. Louis, Missouri, and colleagues for the Ocular Hypertension Treatment Study (OHTS) Group. "It is estimated that 4% to 7% of the US population older than 40 years has OHT. There is substantial controversy on how to manage this large group of individuals who are at higher risk of developing glaucoma than the general population."
The goal of the study was to compare the safety and efficacy of earlier vs later treatment in reducing the risk for POAG in 1636 individuals with ocular hypertension, with baseline IOP ranging from 24 to 32 mm Hg in 1 eye and 21 to 32 mm Hg in the other eye. Participants were randomly assigned to observation or to receive topical ocular hypotensive medication. In the medication group, median duration of treatment was 13.0 years, whereas the observation group had a median duration of 7.5 years without treatment and then received medication for a median of 5.5 years.
To evaluate whether delaying treatment was associated with any harms, the investigators compared the cumulative proportion of participants who went on to have POAG in the original observation group and in the original medication group at a median follow-up of 13 years.
Overall, this proportion was 0.22 in the original observation group (95% confidence interval [CI], 0.19 - 0.25) vs 0.16 (95% CI, 0.13 - 0.19) in the original medication group (P = . 009), or a 27% reduction in glaucoma risk associated with early treatment. For participants at the highest tertile of baseline risk for the development of POAG, based on age, corneal thickness, and baseline IOP, the cumulative proportion of participants who went on to have POAG was 0.40 (95% CI, 0.33 - 0.46) and 0.28 (95% CI, 0.22 - 0.34), respectively.
"There was little evidence of increased adverse events associated with medication," the study authors write. "Absolute reduction was greatest among participants at the highest baseline risk of developing POAG. Individuals at high risk of developing POAG may benefit from more frequent examinations and early preventive treatment."
Limitations of the OHTS study include choice of a target IOP reduction of 20% from baseline, design not that of an epidemiologic study, use of very high thresholds for diagnosing POAG, and use of a convenience sample vs a population-based sample.
"We believe individualized assessment of the risk of developing POAG will be useful to patients and clinicians for deciding on the frequency of examinations and tests as well as the possible administration of preventive treatment," the study authors write. "Clinicians need to consider the patient's age, health status, life expectancy, and personal preferences when making such decisions. Ultimately, the full extent of the penalty for delaying treatment will require longer follow-up to ascertain the incidence and degree of visual impairment by randomization group."
In an accompanying editorial, Alfred Sommer, MD, MHS, from Bloomberg School of Public Health at Johns Hopkins University in Baltimore, Maryland, notes that clinicians should consider whether treating patients with IOP might do more harm than good.
"In the end, the physician is stuck with the persistent problem of whom to treat and whom to watch," Dr. Sommer writes. "The fascinating article by Kass et al provides interesting insights as to many of the issues at stake, but offers little definitive information to guide us. It probably still makes sense that young patients with lots of high risk factors should receive prophylaxis, while elderly patients with few risk factors should not. The endless symposia and debates on how best to manage patients with ocular hypertension will probably continue unabated."
The National Eye Institute and the National Center on Minority Health and Health Disparities, National Institutes of Health; Merck Research Laboratories; Pfizer Inc; and Research to Prevent Blindness supported this study. The study authors and Dr. Sommer have disclosed no relevant financial relationships.
Arch Ophthalmol. 2010;128:276-287.
