Clinical Features of Congenital and Developmental Cataract in East China: A Five-year Retrospective Review

Congenital/developmental cataract is a significant cause of blindness in children worldwide. Full knowledge of clinical features is essential for early diagnosis and proper treatment to prevent irreversible visual impairment. We conducted a retrospective chart review on 520 congenital/developmental cataract cases based on a five-year clinical data from Eye and ENT Hospital of Fudan University, Shanghai, China. Clinical features including age at the surgery, chief complaints, interval between initial identification of cataract-related manifestations and surgery, etc. were summarized. 56.3% of children were bilateral. The age at surgery ranged from 0.25 to 17.4 years, only 9.2% receiving surgery below 1 year. Interval between initial identification of manifestations and surgery ranged from 2 days to 17 years. Concomitant congenital abnormalities were present in 67 patients, with persistent hyperplastic primary vitreous and congenital heart disease as the most frequent ocular and systemic disorders. Strabismus and nystagmus were seen in 20.6% and 11.9% of patients. In bilateral cataract patients with strabismus, axial lengths of esotropia-affected eyes were statistically shorter than exotropia-affected eyes. These findings provide information on characteristics of congenital/developmental cataract in China and may assist in achievement of comprehensive treating strategies in these cases.

Chi-square test). Chief complaints reported by parents or children themselves at admission were obvious leukocoria, significant decrease in visual acuity, or strabismus, which respectively accounted for 38.8%, 41.3%, and 18.1% of all the children. And 9 children came to our hospital with the complaint of occasional identification of cataract by the vision screening at school. Tables 1 and 2 separately showed the distribution of age at surgery and the interval between the first identification of cataract-related manifestations and surgical treatment in congenital/developmental cataract patients reviewed in this study. As indicated, 9.2% (48/520) of patients received cataract surgery within the first year since birth and 56.2% (292/520) of patients aged one to five years old when having the surgery. Interval between initial identification of cataract-related manifestations and surgery ranged from 2 days to 17 years. Only 6.9% (36/520) received timely surgical treatment within one month since the identification of abnormal manifestations, 49.8% (259/520) waited for one to five years for the treatment and 20% (104/520) even waited for more than five years for the surgical treatment.
Axial length. Axial lengths in the affected eyes of unilateral cataract children were statistically longer than those of the fellow eyes: 22.30 ± 1.87 mm versus 22.08 ± 1.29 mm (P = 0.032, Paired-sample t test). Axial length difference between the cataractous eyes and the fellow eyes was positively correlated with the interval between diagnosis and cataract surgery (Correlation coefficient: 0.153, P = 0.034, Spearman Correlation). While in cases of bilateral cataract, no statistically significant difference was seen between axial lengths of both eyes: Ocular and systemic abnormalities accompanying cataract were listed in Table 3. The most frequently seen ocular abnormalities were persistent hyperplastic primary vitreous (PHPV) and retinochoroidal coloboma. All the PHPV presented in the affected eyes of unilateral cataract, with statistically shorter axial length than non-cataractous eyes ( Besides, of all the patients, 11.9% (62/520) had nystagmus. Bilateral cataract eyes were accompanied with statistically more nystagmus than unilateral cataract (P < 0.001, Chi-square test). Additionally, there were 5.2% (27/520) of patients who had both strabismus and nystagmus, 20 of which had bilateral cataract.

Surgical techniques and visual outcomes.
Of 520 children, 418 (80.4%) underwent cataract extraction and anterior vitrectomy with primary intraocular lens (IOL) implantation. 76.4% of implanted IOL were Acrysof SA60AT single-piece IOL (Alcon, Texas, USA) and 23.6% were Tecnis ZCB00 one-piece IOL (Abbott Medical Optics, California, USA). Seven children with posterior polar cataract were reported to have an inevitable posterior capsular rupture during cataract extraction, which were successfully managed by anterior vitrectomy. And iris of two children were accidentally injured during surgery due to the microcoria, yet were also well managed intraoperatively. Totally only 265 (50.9%) children cooperated in both preoperative and postoperative visual acuity tests, aged 7.86 ± 4.11 years averagely. And in this proportion of children, visual acuity was averagely 1.02 ± 0.54 LogMAR before the surgery and improved to 0.64 ± 0.43LogMAR at the first postoperative day.

Discussion
Understanding the preoperative clinical features of congenital/developmental cataract is very useful for the planning of comprehensive treatment strategies of this vision threatening eye disease. However, studies in large sample size are rare in Asian countries, especially in China. The Eye and ENT Hospital of Fudan University is the largest tertiary referral center for children in East China, which receives almost all the pediatric cataracts in this region. Based on the five-year clinical data of pediatric cataracts in our center, we summarized the common clinical presentations of congenital/developmental cataract in east China.
Timely clinical interventions for pediatric cataracts are of prime importance for good visual outcomes. Significant correlation between the axial length difference of affected and fellow eyes and the time since the initial identification of cataract-related manifestations in unilateral cataract children was found in our study. Although weak with the coefficient of 0.153, it still implied that timely treatment was important to reduce the imbalance between the ocular developments of two eyes, which may require further verification in larger sample size. Besides, as Hartmann et al. reported, younger age at cataract surgery contributed to better visual outcomes in congenital cataracts 6 . However, in our study population, no children received cataract surgery within two months since birth, similar to the findings as reported by You et al. in ref. 7. Perhaps due to the different onset ages of developmental cataract, the distribution of age at surgery in our study was quite scattered.
As for the interval between the initial identification of cataract-related manifestations and surgery, only 30.2% (≤1 m: 6.9%; >1 m-1y: 23.3%) of the patients had surgery within one year, while others experienced longer delay, 20% even more than five years. According to the chief complaints shown in medical records, 98.2% (38.8% + 41.3% + 18.1%) of children had suffered from obvious leukocoria, significant decrease in visual acuity, etc. for varying durations ranging from 2 days to 17 years. Hence, it could be seen the vast majority of congenital/ developmental cataract children in East China experienced delay in proper treatment. This phenomenon might be in part due to the lack of sound vision screening system for children in China and might be also attributed to the regional or family economic woes, since the accessibility to cataract surgery was closely related to economy, as indicated by multiple epidemiological investigations worldwide 8,9 . Moreover, low level of economic circumstances is very likely to be consistent with low level of health education, resulting in parents' unawareness of children's abnormal manifestations, which may also lead to the prevalent delay of the illness. Given that the east area  is the most developed part of China, patients in other less developed regions were very likely to experience much longer delay in treatment and consequently more undesirable prognosis.
In the study population, we found 12.9% with congenital comorbidities, oculopathies accounting for 74.6% of them. Seventeen patients were identified with monocular PHPV with the shorter axial length in the affected eye and the corresponding prevalence was 3.3%, occurring the most times among all the concomitant congenital oculopathies, which was consistent with results from previous studies, such as 2.0% reported by Toshiyuki et al. in Japan 10 , 3.8% reported by Yang et al. in Taiwan 5 and 3.0% reported by Plager et al. in the USA 11 . The second most common concomitant oculopathy was retinochoroidal coloboma, a rare ocular malformation resulting from defective closure of the embryonic fissure in our study, with a prevalence of 2.5%, suggestive of abnormal embryogenesis associated with congenital cataracts 12 . Besides, microcornea or microphthalmos were found in 1.9% of our cases (2.3% of cataractous eyes), similar to the 1.67% reported by Lin et al. in Guangdong Province, the southern part of China 13 and lower than previous reports of 8.6% by Toshiyuki et al. 10 With regard to associated systemic disorders, congenital heart disease was the most frequent systemic abnormality; cleft lip and palate came second in our study. Toshiyuki et al. 10 found that prevalence of associated systemic problems was significantly higher among children without family history of cataract than those with, which was not identified in our study.
Another aspect was that larger proportions of patients were identified with ocular disorders such as strabismus and nystagmus. The prevalence of strabismus in our study was 20.6%, which was similar to 19% reported by Fakhoury et al. in France 14 , but was lower than the report of 28% by Kim et al. in Korea 15 and higher than the report of 9.5% by Lin et al. in Guangdong Province of China 13 . Dermirkilinc et al. reported that unilateral cataract cases in children were more prone to develop strabismus 16 , which was not identified in our study. More exotropia was seen in the cataractous eyes of unilateral cataract patients, while in patients with bilateral cataract, esotropia was more prevalent. In those with unilateral cataract along with exotropia, a possible explanation was that the cut off from essential light due to cloudy lens in the early age retarded the normal development of retinal function and corresponding striate cortex circuitry in infants, which left the cataractous eye exotropic, as Frank et al. 17 reported infants did not start to show convergence until six weeks of age. One interesting finding about axial lengths of strabismic eyes was that among bilateral cataract patients with strabismus in our study, axial lengths of esotropia-affected eyes were shorter than exotropia-affected eyes. This agreed with finding of Kim et al. 18 that among patients with sensory horizontal strabismus, axial length was somewhat longer in exotropia group. And similarly, Tanaka et al. 19 reported in their study that among patients with extremely long axial length concomitant with strabismus, exotropia was much more frequently seen. Additionally, nystagmus was found in as many as 11.9% of patients. More nystagmus was seen in bilateral cataract due to severer vision impairment compared to unilateral cataract. Both strabismus and nystagmus were signs of severe vision deprivation early in life 20 , indicating unfavorable visual outcomes of cataract patients with these disorders. Particularly for the 5.2% patients with both strabismus and nystagmus in our study, prognosis might be even worse.
In conclusion, even in the developed east China, patients diagnosed with congenital/developmental cataract were very likely to experience delays in treatment. Concomitant abnormalities are frequently seen in congenital/developmental cataract patients, which should be taken into consideration for making comprehensive treating strategies.

Patients and Methods
The Institutional Review Board of the Eye and ENT Hospital of Fudan University, Shanghai, China approved this retrospective chart review, which was affiliated to Shanghai Pediatric Cataract Study (registered at www.clinicaltrials.gov, accession number NCT03063216). All procedures were conducted in agreement with tenets of the Declaration of Helsinki. Written consent forms were acquired from guardians of the patients for the use of their medical data for research purpose.
Patients and clinical records reviewed. We reviewed medical records of congenital/developmental cataract patients who underwent cataract extraction with or without IOL implantation between April 2009 and April 2014 in our hospital. Those with complete medical records were eligible for inclusion.
Basic information of the patients including gender, family history, laterality, chief complaints, the age at surgery and the interval between the initial identification of cataract-related manifestations and surgery were reviewed.
Preoperative examinations of congenital and developmental cataract children included visual acuity test, slit-lamp examination through dilated pupil for the confirmation of diagnosis, axial length measurement by IOLMaster or intraoperative applanation A-scan ultrasonography for the calculation of IOL power, and B-scan ultrasonography for the inspection of posterior segment abnormalities. Preoperative visual acuity, axial length and concomitant congenital abnormalities including oculopathies such as strabismus and systemic disorders were analyzed.
All the surgeries were performed under general anesthesia. For children who underwent cataract extraction by irrigation/aspiration device, surgical procedures were mainly making scleral tunnel incision, continuous curvilinear capsulorhexis, and cataract removal. A foldable IOL was primarily implanted into the capsular bag in selected cases. And no matter with IOL implanted or not, posterior capsulotomy and anterior vitrectomy were finally performed using a 23 G/25 G vitrectomy instrument. For children who underwent cataract extraction by 23 G/25 G vitrectomy instrument, surgical procedures were mainly making limbal incisions by a 23/25 G trocar with a microcannula, central capsulotomy, and cataract removal. And foldable IOL was primarily implanted into the capsular bag in selected cases. No matter with IOL implanted or not, posterior capsulotomy and anterior vitrectomy were then performed using the vitrectomy instrument. Surgical techniques used and the percentage of IOL implantation in these children was summarized as well as surgical complications. Besides, visual acuity on the first postoperative day were routinely documented and also analyzed in our study. Visual acuity results were converted to the logarithm of the minimum angle of resolution (LogMAR) for analysis.