Penetrating keratoplasty in children under 3 years old with congenital corneal opacities

INTRODUCTION

Penetrating keratoplasty (PK) has been the most challenging technique for pediatric and corneal surgeons since its first attempt in 1977 by Waring and Laibson, followed by Stulting in 1984, and Cowden in 1990, where they showed satisfying results. Although the prognosis is not as good as in adults, PK is still considered as the first step preventing irreversible loss of visual function in a child due to amblyopia.Several indications for pediatric PK, including congenital causes of corneal opacities, acquired traumatic and nontraumatic corneal opacities cases.

Early PK is mandatory to achieve optimal visual development and prevent the incidence of amblyopia. The prevalence of congenital corneal opacities is approximately 3/100 000. The leading cause of congenital corneal abnormalities in developed countries is Peter’s anomaly (40.3%), followed by sclerocornea(18.1%), dermoid cyst (15.3%), microphthalmia (4.2%),birth trauma and metabolic diseases (2.8%). Studies reported previously that the range of indication for paediatric PK in cases of congenital diseases lasts from 14% to 64%, while in acquired non-traumatic condition is from 19% to 80%, and acquired traumatic disorders 6% to 29%.

The visual acuity of 7 eyes had improvement post keratoplasty,while six eyes were equal to pre-graft, and three eyes had reduced vision due to the effect of graft failure. In addition,the visual acuity of bilateral CCO, which the PK was done on both, had better outcomes than the unilateral CCO. The visual acuity pre- and post-graft analysis using the Wilcoxon test indicates not significant (=0.34). Nonetheless, 44% had improvement in visual outcomes after PK (Figure 4).A successful PK was performed in a girl with CCO on both of her eyes (Figure 5A). The keratoplasty was done one by one following the availability of the eye donor, in which the left was performed first. We managed the surgery on the right eye eight months later (Figure 5B, 5C). The evaluation six months later showed clear grafts on both eyes with no signs of rejection and graft failure (Figure 6).

公募基金公司的分級基金業務在2015年的股災后就已經基本停滯。而在這次資管新規中，公募產品和開放式私募產品被明令禁止不得進行份額分級，曾經一度火爆的分級基金被判了死刑。明確了現有的分級基金品種也一樣要在過渡期后壽正終寢。看來，監管層對2015年分級基金引發的“鬧劇”，比如下折造成投資者巨虧的歷史記憶猶新，這類規則比較復雜的金融產品也確實不適合普通的投資者。不過這樣一來，市場上現有的分級A中的折價品種，或許存在一些折價收斂帶來的投資機會。

Thus, this study aims to evaluate the survival of graft rejection and visual outcomes in five years of follow-up after PK in the presence of various congenital corneal abnormalities in children age less than three years old in Jakarta Eye Center.

SUBJECTS AND METHODS

The importance of pre-operative care is to assess the possible benefits of the surgery outweigh the potential risks and all alternatives of PK have been considered. The evaluation of pre-operative care comprised slit-lamp handled, tonopen, B scan Ultrasonography, fundus retcam, cornea diameter measurement, ERG-VEP, and retinoscopy. For a severe microcornea found during slitlamp examination, then the PK was not advised. In case of cataract, the surgery can be done along with keratoplasty.An ocular pressure above 20 mm Hg found during the IcarePRO tonometer examination should be referred to a glaucoma specialist. The ocular pressure and cornea diameter measurement can be evaluated under anaesthesia, or referred to as evaluation under anaesthesia (EUA). The ERG-VEP was done in EUA to evaluate the function of retina and brain.The results were then consulted to neuro-ophthalmologist to decide whether PK should be done or not. Retina examination is under B scan to evaluate the posterior segment. Retcam was done after keratoplasty to assess in case of opacity in the posterior segment. Afterwards, retinoscopy was done with dilated pupil.

Our study included children under three years old,referred by a pediatric ophthalmologist, which then cornea transplantation was performed by the cornea surgeon, between the year 2014-2019 in Jakarta Eye Center (JEC). The data were collected by a retrospective review of the patient’s medical record with a cohort study design. Children with congenital corneal abnormalities were indicated to undergo surgery.

The ethical approval of this study was given by the Ethic Committee of Jakarta Eye Center and the consents were approved during the informed consent prior to surgery.

All cornea donors were from Santa Lucia Eye Bank, Philippines. The collected donor age was ranged from 17 to 23 years old. The cornea donor size was range of 7-7.5 mm in diameter. The regular cornea size of the recipients was expected to be ranged from 6.5-7 mm. The host-graft disparity was counted as 0.25-0.50 mm.

All surgeries were performed under general anesthesia. The initial step was to remove the recipient’s cornea by partial thickness trephination. A careful excision of the cornea was performed with curved corneal or Vannas scissors. Manual iridectomy was created in the upper iris to prevent the risk of glaucoma later after surgery.A viscoelastic was then required to reform the anterior chamber and protect the iris-lens. The graft was secured using 16 interrupted 10-0 nylon sutures with knots buried.Subconjunctival corticosteroid injection and topical antibiotics were given at the closure of surgery (Figure 1).

Our study suggested pre and post keratoplasty was not significantly improved (that although the visual acuity=0.34), the graft survival rate was found to be promising.The overall mean survival time is 22mo (standard error 2.419),with a survival rate of 83.3% int one year. Although there is a gap between the aged of timing PK, we provide the possibility of improving the visual acuity (44%) with good survival.Moreover, we did achieve our main purpose to stabilize the visual function to prevent blindness. Since the patients in our study were below three years old, even with the following object or light fixation only is satisfying. Ⅰn conjunction with our study, we found this to be similar to the previous studies mentioned above.

The visual acuity and graft survival rate in 6, 12, and 18mo were evaluated by descriptive statistics using percentages. We used Kaplan-Meier to present the graft survival plots showing the association between rejection and age. The survival curve included were age below 24mo and above 24mo when the PK was performed. The visual acuity before and after PK was also analyzed using Wilcoxon signed ranks test.

2.2.5.3 發病條件。在日照充分、土壤干旱、晝夜溫差大、多風等條件下易發生。此病發生適溫為20～28 ℃，最適相對濕度為52%～75%。海拔較高、晝夜溫差大、多風條件有利于此病的發生。

RESULTS

PK was performed in sixteen eyes from eleven patients,comprised of seven girls and four boys within 3 to 36 months old. The median age of the first visit was 12 months old.When the surgery was done, it was 14 until 56 months old,with a median age of 20.5 months old. The follow up was then conducted for patients four months after the surgery until 36mo post PK with the median time of 14.5mo. The total length of follow up was 12 to 55mo. The measured mean IOP was 16.5±3.9 mm Hg (Table 1).All cases had congenital corneal opacification (CCO) with or without microcornea. Of all the patients, four had unilateral CCO, while seven cases were bilateral. PK was performed on both eyes of five cases of bilateral CCO. However, two eyes had severe microcornea, hence the surgery was not advised (Table 1).Thirteen eyes of sixteen operated eyes showed clear grafts with no rejection in the next following months. The three grafts rejection manifested 7 to 13mo after the PK. The graft survival rate of the first 6, 12, and 18mo later of keratoplasty was 100%,83.3%, and 66.7%, respectively, from 14 eyes (Figure 2). The two eyes had times of follow up before six months were excluded consequently. The subsequent two until 21mo, additional cataract surgeries were done in 7 eyes, which had developed a cataract. The other two eyes had band keratopathy after 10-and 24-months post keratoplasty. A scleromalacia occurred in one eye of a patient with cataract 23mo after surgery (Table 1).The graft survival on Kaplan-Meier showed the time of rejection after the grafts were implanted (Figure 3). The groups were divided based on the type of rejection. Eventually, 7 eyes showed no rejection and graft failure at the given time.However, further follow-up not conducted later. Overall,the graft failures occurred in 50% of the operated eyes and post-surgery complications included cataract 43.7%; band keratopathy 12.5%, and scleromalacia 6.25%. However, the overall mean survival time based on the aged timing of surgery before and after 36mo is 22mo (95% confidence interval,standard error 2.419) and no significant difference between the patient’s age underwent PK before and after 36mo of their age(=0.52).

劉志武似乎與他較上勁，冷笑說：“我們查過寄存記錄，行李寄存處都是先付費，后取行李，兇手——不，應該說是寄尸者——因為我們還不能確定兇手就一定是寄尸者，先行預付了三天的寄存費，這么熱的天，以寄尸者的縝密思維，他難道不知道尸體會發臭嗎？這說明，寄尸者或者是兇手早就有預謀的。”

The clinical outcome of PK varies from visual development and restoration, clarity of the graft, risk of rejection and infection, which indicates that corneal transplant is essential.During the period of visual development, visual rehabilitation is required after customized clinical and surgical management to overcome the significant challenges associated with pediatric keratoplasty. In terms of facing the unique challenges of pediatric PK, the importance of pre-operative, intraoperative,and post-operative care should be considered.

DISCUSSION

The development of visual acuity is critical, especially during rapid development in early ages, starting from neonates until the first six months of life. Vision development remains important during preschool years and affects the latter outcomes. Therefore, congenital disorder and trauma disrupt the process of development that would impact the visual system. One of the leading causes of congenital disorders that affect the vision in children is CCO. Thus, the primary aim of pediatric keratoplasty is to improve their visual acuity that was disrupted due to opacity.A study by Zhangreported that the most common indication of PK for children under 12 years old was CCO.The patients were categorized as infants (≥3mo and <4y) or children (≥4y and ≤12y). Ⅰn our study, most patients came within the age of 12 to 36mo. Only five patients came before six months of age. Most parents may not recognize the signs and symptoms as they came later at age 12mo. However,the keratoplasty was done at six months up to a year after the initial visit due to the availability of the eye donor. Most PK was done during infants, while the other three eyes were performed in 42, 46, and 56mo.

A study in Mexico showed the mean graft survival time was 45.6mo (95% confidence interval 31.8-58.4mo, standard deviation 0.069), with a survival rate of 70% at one year.Univariate Cox proportional hazard showed that being<9 years of age at the time of the surgery (=0.023) and corneal dystrophies (=0.04) were prognostic factors for corneal rejection. A 10-year study in Malaysia reported that 18.75% of children who underwent PK were successfully achieved the best-corrected visual acuity of 6/12 or better. A hazy graft was noted in 68.75% of patients and was attributed to graft rejection, glaucoma, and graft failure. Factors contributing to the graft’s survival rate at a one-year postoperative period include the presence of vascularized cornea,intraocular inflammation, and combined surgery, which were significant (<0.05).

為避免城鎮用水過度緊張，可以建立企業用戶用水優先權制度。對于新增加的城鎮企業用水戶，必須按照取得用水權的先后順序、排在老用戶之后用水，也就是說老用戶擁有優先權，如果水不夠用，應先停后來者的用水。這樣想要進入城市的企業就要慎重考慮供水風險。這既可以保護老用戶的利益、降低已有投資的風險，又可避免缺水城市過度膨脹。……