Photopic pupil size change in myopic orthokeratology and its influence on axial length elongation

INTRODUCTION

Myopia is a globally public health problem associated with increased ocular-related morbidity and enormous healthcare costs

. In recent decades, it’s prevalence in adolescents has already been increasing to 10% to 25% in industrialized societies of the West and 60% to 80% in East Asia, respectively

. The myopic prevalence will even significantly increase to 50% of the world’s population by 2050

. Overnight orthokeratology (ortho-k) has been considered an effective and safe myopia-retarding therapy to decrease the increasing prevalence of high myopia and the potentially blinding myopic complications, such as retinal detachment, macula choroidal neovascularization and glaucoma. Although the mechanism of ortho-k remains controversial, most previous studies, including randomized and controlled clinical trials, have demonstrated that ortho-k reduces the axial elongation by 40% to 60% in children when compared with single-vision spectacles or soft contact lenses

.

In the long-term clinical experience, we found the myopia control effect of ortho-k displayed a large inter-individual variability and cannot be precisely predicted. Increased knowledge of factors related to axial elongation and myopia progression in ortho-k is of great importance, especially for the pre-wear evaluation. If the accurate benefit gained from ortho-k wear could be predicted, we can select different appropriate strategies, such as 0.01% atropine

, or optimize lens design according to the specific eye characteristics in children to improve the retardation effect of ortho-k and ultimately achieve personalized myopia intervention. Although we have been interested in the predictors of ortho-k treatment for almost 10y,the result is always exciting and controversial. Recently, one study has reported that changes in corneal aberrations could be the inhibitory factor of ortho-k on myopia progression

.However, in another research, neither short-term nor long-term changes in corneal aberrations were significantly correlated with the 2-year change in axial elongation

. Chen

found large pupil diameters facilitate larger axial retardation effect in myopia treated with ortho-k. However, Downie and Lowe

revealed in their study that pupil size appeared not to influence the rate of myopic progression in ortho-k treated eyes.In 2007, a longitudinal study first reported an association between more time outdoors and a reduced risk of myopia onset

. After that, a series of observation, from animal experiments to human clinical trials, suggest that outdoor light exposure might be a modifiable risk factor for myopia onset

. Based on such finding, several years ago, education department has renovated the illumination of classroom in some schools in Shanghai and encourage children to participate in outdoor activities in order to reduce the incidence of myopia.Hence, a photopic condition would more often occurs in daily life conditions in most children and adolescents during ortho-k treatment. Compared with the scotopic pupil diameter (SPD)assessed in Chen

’s research

, we deduce that photopic pupil diameter (PPD), which was not so stable and would be affected by illumination condition, would be more valuable in predicting myopia control effect in ortho-k treatment.

Cycloplegic manifest refraction was performed only at enrollment. One drop of 0.5%tropicamide was instilled in each eye five times at 5-minute intervals, and autorefraction was measured three times after 30min. At the rest follow up visit, only non-cycloplegic subjective refraction were conducted.

Whether pupil diameter was the factor that suppress myopia progression in children treated with ortho-k is still controversial. A study done by Chen

demonstrated the relationship between the basic SPD and regulation effect, found that larger SPD turned out to have less myopia progression in ortho-k treated eye. However, in two latter studies, no association was found between pupil size and myopia control effect in eyes undergoing ortho-k treatment

. In the current study, PPD

showed significant correlations with axial elongation. Unexpectedly, we got exactly the opposite result that smaller PPD

experienced smaller axial elongation in ortho-k lens wearers. At the end of the 1-year period, AL change in the ortho-k subjects with PPD below or equal to 4.81 mm was approximately half that of the ortho-k subjects with PPD above 4.81 mm. The different result can be attributed to that we measured the PPD, while Chen

assessed the SPD in their study. Due to the SPD cannot reflect the real state of daily life conditions, Chen

deduced the PPD in their study from the scotopic one, according to the research of Alfonso

that the average difference between photopic and mesopic pupil size was approximately 1.5 mm and finally draw the conclusion that children with relatively larger pupils would benefit more myopia control effect from ortho-k treatment

. However, in the article of Alfonso

,they also revealed that there is no potential mutual predictive ability between PPD and SPD because the photopic value only explains 48.1% of the variability in the mesopic value, Hence,any prediction of mesopic pupil size from photopic values would be inaccurate. They recommended to measure photopic and scotopic pupil size respectively in order to obtain reliable value. Considering that photopic pupil size is unstable, we got 5 repeatable PPD data for each eye under uniform illumination conditions and used the averaged values for analyses in order to obtain an unbiased value of pupil diameter. Therefore, the result of the current study that AL is prone to increase slowly in subjects with a photopic small pupil diameter by ortho-k was convincing.

我沿著山勢拾階而上，歲月的痕跡與湖湘文化的積淀就林立在這山間，文廟、湘水校經堂、船山祠、濂溪祠、屈子祠等紛紛闖入我的眼簾，繁華薈萃的湖湘文化和層林盡染的山中風景讓我應接不暇。濂溪一脈的理學自湘南至此發揚光大，隨著湘江一起浩蕩地流向大半個中國。工善其事、業精于勤的湖湘偉人站在歷史巨浪的潮頭，魏源在和林則徐徹夜長談后伏案寫下《海國圖志》，讓國人睜眼看世界；曾國藩從雙峰老家帶著幾百家勇橫掃中國，挽狂瀾于既倒、扶大廈之將傾；熊希齡帶著湘西人的赤誠和堅韌從鳳凰來此求學，最后成了北洋政府國務總理，正所謂：此君一出天下暖。

SUBJECTS AND METHODS

Subjects in the ortho-k group were fitted with 4-zone lenses(Euclid Systems Corporation, Herndon, USA) made of Boston EQUALENS II (oprifocona) with a nominal Dk of 127×10

(cm

?mLO

)/(s?mL?mm Hg), a diameter of 10.6-11.0 mm, an optical center thickness of 0.21-0.23 mm,a wetting angle of 36°. Lenses were fitted according to the instructions recommended by the manufacturer. Final lenses were determined after optimization regarding fluorescein pattern, topographical evaluation, refractive and visual outcomes. The subjects were provided with clear instructions regarding the wearing and maintenance of lenses. Follow-up appointments were promptly planned.

This longitudinal, prospective and nonrandomized study was conducted at Shanghai Eye Disease Prevention & Treatment Center and registered at Clinical-Trials.gov (NCT03516357). The study followed the tenets of the Declaration of Helsinki and was approved by the Ethical Committee of the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine. All subjects, and their parents, provided signed written informed consent for treatment and were fully informed of the risks and benefits of the treatment.

A total of 202 patients (92 males and 110 females)were enrolled based on the inclusion criteria listed in Table 1.All subjects accepted detailed medical history taking and a series of prescreening ocular examinations, including slit-lamp microscopy of the anterior and posterior segment, cycloplegic manifest refraction, corneal topography (Oculus, Wetzlar,Germany), and binocular vision assessment.

Subjects were instructed to wear ortho-k lenses every night with a minimum of 8h per night and were examined 1, 7, 30 and 90d after beginning ortho-k treatment. After the initial 90d, subjects were examined every 3mo. All examinations were fulfilled within 2h of removing the lens (between 8 and 10

)to minimize the potential influence of diurnal variation. At all follow-up visits, visual acuity, slit lamp examination, manifest refraction, corneal topography was performed. Subjects were also examined whenever an abnormal symptom occurred.

低溫等離子體凈化法的原理是在外加電場的作用下，通過介質放電產生大量的高能粒子，高能粒子與有機污染物分子發生一系列復雜的等離子體物理-化學反應，從而將有機污染物降解為無毒無害的物質[16]；該法是一種新型的凈化工藝，可以處理甲苯廢氣等。低溫等離子體凈化法適用于處理VOCs質量分數低（1～1000 μL/L）的有機廢氣，與傳統方法相比具有處理效率高、反應流程短等優點，但該技術還不成熟，容易造成二次污染，且能耗較高。

In the spectacle group, examinations were performed every 6mo until the end of the study period.

水稻在生長期間易感染白葉枯病，使稻谷不飽滿，直接影響大米質量。水稻感染白葉枯病會出現葉片枯萎的情況發生，由此可以看出，白葉枯病的感染部位主要是在葉部，如果根莖葉出現了破損，病毒會從破損處對水稻造成破壞。……