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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 15  |  Issue : 1  |  Page : 20-25

Congenital rubella syndrome and its postoperative visual outcome: A prospective longitudinal study in a tertiary care hospital in eastern India


1 Department of Ophthalmology, I.P.G.M.E and R and SSKM Hospital, Kolkata, West Bengal, India
2 Department of Ophthalmology, Chinsurah District Hospital, Hugli-Chuchura, West Bengal, India
3 Department of Ophthalmology, Nandigram Superspeciality Hospital, Nandigram, West Bengal, India

Date of Submission08-Jul-2021
Date of Decision21-Sep-2021
Date of Acceptance27-Oct-2021
Date of Web Publication24-Jan-2022

Correspondence Address:
Dr. Mahesh Chattopadhyay
Riddhi Siddhi Garden, Riddhi Apartment, Flat No 2e.Opposite To ESI Joka Hospital, Kolkata - 700 104, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kleuhsj.kleuhsj_186_21

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  Abstract 

BACKGROUND: Congenital rubella syndrome is a threatening consequence of rubella infection in pregnancy characterized by the triad of cardiac, ocular & hearing defects. The morbidity and financial load associated with congenital rubella syndrome have an adverse effect on the quality of life.
AIMS and OBJECTIVES: To evaluate the postoperative visual outcome of congenital rubella cataract and assessment of the immediate postoperative complications.
MATERIALS AND METHODS: Institution-based longitudinal prospective observational study was carried out among 21 patients aged 1 month to 6 years of both sex groups with congenital rubella cataract. A single surgeon performed phacoaspiration and anterior vitrectomy. Intraocular lens implantation was done in children aged >2 years where the rest were kept aphakic. Best-corrected visual acuity and immediate postoperative complications were assessed in all cases preoperatively and at 1 week, 4 weeks, and 6 months postoperatively.
STATISTICAL ANALYSIS USED: Data were entered into Excel and analyzed by SPSS (version 25.0; SPSS Inc., Chicago, IL, USA) and Graph-Pad Prism version 5.
RESULTS: The study evaluated 28 eyes of 21 patients. The mean age of the study population was 21.1 ± 20.27 months with male predominance (1.625:1). Among 28 eyes only 10 eyes (35.71%) single-piece acrylic hydrophilic intraocular lenses were implanted and the rest 64.29% were kept aphakic. Immediate postoperative complications were noted such as anterior uveitis(9 eyes), corneal edema(3 eyes), striate keratitis(6 eyes) with more predilection towards aphakic patients & rest had no significant complications. At 6 months follow-up, significant improvement of best-corrected visual acuity (≥6/60) was noted in 52.38% of eyes which was about 5.12% pre-operatively ('P' value <0.01).
CONCLUSION: Significant improvement in visual outcome was noted with early diagnosis and intervention with acceptable rate of immediate postoperative complications.

Keywords: Aphakia, congenital cataract, pseudophakia, rubella, toxoplasmosis, other agents, rubella, cytomegalovirus, herpes simplex screening


How to cite this article:
Srivastava SR, Mazumder J, Chattopadhyay M. Congenital rubella syndrome and its postoperative visual outcome: A prospective longitudinal study in a tertiary care hospital in eastern India. Indian J Health Sci Biomed Res 2022;15:20-5

How to cite this URL:
Srivastava SR, Mazumder J, Chattopadhyay M. Congenital rubella syndrome and its postoperative visual outcome: A prospective longitudinal study in a tertiary care hospital in eastern India. Indian J Health Sci Biomed Res [serial online] 2022 [cited 2022 May 20];15:20-5. Available from: https://www.ijournalhs.org/text.asp?2022/15/1/20/336298




  Introduction Top


Congenital rubella syndrome (CRS) is a threatening consequence of rubella infection in pregnancy characterized by the triad of cardiac, ocular, and hearing defects.[1] The eye complaints are often congenital cataract, congenital glaucoma, microphthalmia, and oculomotor disorder which need to be screened early and intervened.[2] Worldwide, it is estimated that there are more than 100,000 infants born with CRS each year.[3] The burden of disease is ponderous on society, so vaccination and other preventable strategies should continue and be strongly encouraged.[4]

Aims and objectives

  1. To assess the visual outcome of congenital rubella cataract after surgery
  2. To evaluate the immediate postoperative complications.



  Subjects and Methods Top


Study area

This study was conducted at the Department of Ophthalmology, I. P. G. M. E and R and SSKM Hospital, Kolkata, and Department of Neonatology and Pediatrics, I. P. G. M. E and R and SSKM Hospital, Kolkata.

Study population

Patients with congenital cataracts aged between 1 month and 6 years tested positive for rubella antibodies (referred from the Department of Neonatology and Pediatrics).

Study period

The study period was 15 months (January 1, 2019–March 31, 2020).

Sample size

The sample size was 21.

Study technique and data collection

  1. Maternal history taking (by questionnaire method and discharge certificate)
  2. Clinical examination and local eye examination
  3. Toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes simplex (TORCH) screening
  4. Metabolic screening
  5. Relevant investigations (brainstem evoked response audiometry, echocardiography, and serology).


Study tools

  1. Torchlight
  2. Visual acuity chart (central steady maintained method, preferential looking test, optokinetic nystagmus drum test, teller visual acuity card test, and Snellen chart)
  3. Slit-lamp biomicroscope
  4. Direct or indirect ophthalmoscope (to exclude any retinal pathology)
  5. Pediatric speculum (Alfonso speculum)
  6. Anesthetic eye drops and mydriatic eye drops
  7. General anesthesia equipment if required
  8. Streak retinoscope
  9. Perkins tonometer
  10. Castroviejo calipers.


Investigations

  1. Slit-lamp biomicroscopy
  2. Indirect ophthalmoscopy using 20D lens or direct ophthalmoscopy
  3. B-scan ultrasonography (USG) (to measure axial length of eyes)
  4. Biometry in older children
  5. TORCH screening.


Type of study

This was an institution-based longitudinal prospective observational study.

Methods

Detailed antenatal history was obtained by questionnaire method about any gestational illness, drug intake, personal history, vaccination status, and others. All patients underwent thorough ophthalmic evaluation by a trained pediatric ophthalmologist, and all of them were further assessed by a pediatrician, otolaryngologist, cardiologist, and anesthesiologist to exclude systemic anomalies. The collection of peripheral blood (1–2 ml) was done by venipuncture or by a femoral tap with the prior consent of parents or legal guardians of the patients. Sera for immediate use were stored at 4°C and those for delayed use were kept at -20°C (extra samples). Assay of antibodies was done by enzyme-linked immunosorbent assay using commercially available “bioelisa” kits by immunocapture technique. The sera for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies were tested at a dilution of 1:100, along with positive and negative control in each turn. Tests were repeated in parallel at 2 weeks for all positive samples.

Comprehensive ocular examinations were carried out which included visual acuity assessment, fixation pattern, anterior segment evaluation, consisting of Hirschberg test, nystagmus evaluation, corneal diameter measurement, tonometry, identification of type, and morphology of cataract by slit-lamp biomicroscopy, and fundus evaluation by direct and indirect ophthalmoscope. In uncooperative or too young patients, evaluation was done at the time of surgery under general anesthesia. B-scan USG was performed in cases with dense media opacities. Special investigations were advised by an experienced pediatrician for the management of systemic anomalies.

All the cases were operated by a single surgeon. General anesthesia was used in all the patients. The surgical technique of cataract extraction consisted of superior limbal incision, anterior capsulorhexis, hydrodissection, aspiration of nucleus, and cortex. In all cases, posterior capsulorhexis and triamcinolone-assisted anterior vitrectomy were performed. Children under 2 years of age were kept aphakic. Those patients were prescribed aphakic glasses after surgery as soon as possible. Out of 28 eyes of 21 patients (aged between 2 months and 6 years of both sex groups), single-piece foldable acrylic hydrophilic intraocular lenses were implanted in more than 2-year-old patients. Intraocular lens power was calculated using Sanders–Retzlaff–Kraff-II formulae in accordance with the age and axial length. All the intraocular lenses were implanted in the ciliary sulcus.

Postoperative treatment included eye drop prednisolone acetate (1%) tapered over 12 weeks, eye drop homatropine (2%) for 4 weeks, and eye drop moxifloxacin (0.5%) for 4 weeks. Oral steroids (0.8 mg/kg) were given over 2 weeks in tapering dose. Oral analgesics and oral antibiotics were given for 7 days. All patients underwent postoperative evaluation at 1 week, 4 weeks, and 6 months by the same methods before.

Inclusion criterion

  • Patients aged 1 month to 6 years with unilateral or bilateral congenital cataract tested positive for rubella antibodies
  • Their parents or legal guardians signed the informed consent for clinical examinations and management.


Exclusion criterion

  • Patients with congenital or developmental cataracts tested negative in TORCH screening
  • Patients with traumatic cataract and drug-induced cataract
  • Patients with systemic syndromes such as Down syndrome and Marfan syndrome
  • Noncooperative parents or legal guardians.



  Results Top


Statistical analysis

For statistical analysis, data were entered into a Microsoft Excel (Microsoft excel professional 2019) spreadsheet and then analyzed by the Statistical Package for the Social Sciences (version 25.0; SPSS Inc., Chicago, IL, USA) and GraphPad Prism and Prism are registered trademarks of GraphPad Software, Inc. Data had been summarized as mean and standard deviation for numerical variables and count and percentages for categorical variables. A Chi-square test was used for the categorical data, and P < 0.05 was considered statistically significant.

The mean age of presentation was 21.1 months (standard deviation ± 20.27 months). It was also noted that 47.69% of the study population belong to the age group of <1 year. More prevalence was found in males almost in all age groups [Figure 1].
Figure 1: Age–sex distribution of patients

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The most common presenting feature was the diminution of vision in 16 eyes (42%) followed by poor face recognition of mother's face and/or any objects in 12 eyes (31.58%), deviation of eyes in 3 cases (7.89%), white pupillary reflex in 4 eyes (10.53%), and nystagmus in 3 eyes (7.89%). The majority of the patients had two or more complaints (68%) and only 32% present with a single complaint [Figure 2].
Figure 2: Distribution of clinical presentation in the study group

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Most of the mothers (76.2%) of children with CRS had an uneventful gestational period. The most significant complaint which was documented in the antenatal period was having a bad obstetric history (BOH) such as abortions in the first trimester of pregnancy (9.52%). Two of them had a history of fever (9.52%), whereas only one of them had a history of joint pain (4.76%) [Table 1].
Table 1: Distribution of maternal clinical features during the antenatal period

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On evaluation of general condition of patients, cardiovascular defects (33.33%), deafness (28.5%), and skin rash (9.52%) were found in this order. Hepatosplenomegaly and mental retardation were equally distributed (4.76%) among the study group [Table 2].
Table 2: Distribution of systemic features among patients

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Out of 21 cases, the majority (67%) were found to be positive for IgG only. Among the rest, IgM only was found in four cases and both IgG and IgM were found in three cases [Table 3].
Table 3: Distribution of toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes antibody titer among patients (n=21)

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33.33% of congenital rubella cataracts had cardiovascular defects, out of which patent ductus arteriosus (PDA) was most common in the study population (four patients). Few patients with PDA also had other cardiovascular defects such as ventricular septal defect (VSD), atrial septal defect (ASD), pulmonary stenosis (PS), and coarctation of the aorta (CoA). Isolated heart defects were noted in PS, VSD, and CoA.

Among 21 cases, 18 patients had bilateral cataracts, whereas only three patients had unilateral cataracts. Out of 39 eyes of 21 cases, all the unilateral cases (7.69%) were operated. Among bilateral cases, both eyes are operated in nine patients only (46.15%), seven patients underwent surgery in one eye and lost to follow-up for fellow eye (17.94%), one of them was unfit for general anesthesia (5.12%), and one expired due to systemic complication (5.12%). Henceforth, only 28 eyes were operated on among 39 eyes.

Serial monitoring of the postoperative patients was done at 1 week, 4 weeks, and at the end of 6 months. Significant improvement was noted in the visual acuity with a “P” < 0.05 at the end of 1 week and 4 weeks and < 0.01, 6 months following surgery.


  Discussion Top


The association of rubella virus with congenital cataracts has been well-established,[5] and the ocular manifestations of CRS can be detected much earlier than other systemic abnormalities.[6] Usually, the diagnosis of congenital infections depends on serological detection of IgM. However, rubella-specific IgM antibodies are not frequently demonstrated as antibody synthesis is often delayed and may not start until some months following birth in about 25% of cases.[7] The severity of damage to the developing fetus depends upon the virulence of the organism and the timing of infection. Infection in early pregnancy increases the risk of fetal damage. The incidence of birth defects comes around 90% if the infection is contracted within the first 10 weeks of pregnancy.[8]

In our study, 28 eyes of 21 patients underwent cataract surgery. The mean age of the study population was 21 ± 20.27 months, out of which the majority (47.62%) belonged to the age group <1 year [Figure 1]. Masresha et al.[9] study of CRS surveillance in Africa showed that most (43%) were aged 6–11 months, whereas 21 of them were newborns.

Male predominance (61.9%) was noted among all age groups [Figure 1]. Similar male predilection (58.5%) was noted in Indian CRS surveillance 2016–2018 in Murhekar et al.[10] study. However, Vijayalakshmi et al.[11] found the male-to-female ratio as 1.5:1 while we found it as 1.6:1.

Antenatal history was based on a standardized questionnaire to include all necessary details. It was found that more than 75% of mothers had uneventful antenatal history and 23.8% of cases had a history of fever, rash, arthritis, and BOH [Table 1]. Leung et al.[12] published an article that revealed that approximately 25%–50% of postnatally acquired rubella cases were asymptomatic. However, the most common manifestation was arthralgia or arthritis in 60%–70% of teenagers and adult women, following 1 week after the rash. Rubella infection during the first trimester of pregnancy leads to a remarkable increase in the incidence of congenital malformation, stillbirth, abortions, premature labor, and intrauterine growth retardation.[13]

In susceptible pregnant women, the virus may cross the placenta and get transmitted through the vascular system of a developing fetus. In a study by Lahbil et al.,[8] 43.75% had cardiac anomalies, 37.5% had deafness, and 2% had psychomotor disturbances. Norman Gregg, an Australian ophthalmologist, reported an epidemic of congenital cataracts among 78 infants following maternal rubella infection in 1940 in Australia. More than 50% of infants suffered from cardiovascular anomalies such as PDA, ASD, VSD, and PS.[13] However, maternal infection is not suggestive of vertical transmission in 100% of cases. It may not necessarily affect all cases of fetal infection.

Diagnosis of rubella and congenital rubella is usually done by detection of rubella-specific IgM. IgM positivity gradually declines over the 1st year of life and most infants at 1 year of age test negative for IgM. Rubella-specific IgG can persist beyond 6 months (the age when IgG derived from mother would have usually disappeared) in 95% of infants with CRS. The presence of IgG over 6 months of age may indicate either prenatal or postnatal infection. The probability of it being prenatal infection can be assessed by comparing the IgG prevalence among the suspected CRS case with that among age-matched controls.[14] However, it may be difficult to conclude a diagnosis of congenital rubella in children over 3 months of age.[15] Among our study population, 67% were found to be positive for IgG only. Among the rest, IgM only was found in four cases and both IgG and IgM were found in three cases [Table 3]. Dewan et al.[16] conducted a prospective study in 65 under-five children with suspected CRS. It was found that 40% of cases with ocular pathology were positive for anti-rubella IgM and 79% were seropositive for rubella infection (IgM/IgG). Overall, 26% of cases with ocular abnormalities satisfy the criteria of the WHO case definition of CRS. In a study by Singh et al.,[17] children under 6 years of age with congenital cataracts underwent diagnosis using serology and polymerase chain reaction. The IgM positivity of rubella was about 5.8%, and 33% of cases tested positive for rubella in the polymerase chain reaction.

Among 28 eyes operated, 21 eyes were followed up to 6 months as 7 of them did not turn up after 1 month [Figure 3]. Out of 28 eyes in 10 eyes, (35.71%) single-piece acrylic hydrophilic intraocular lenses were implanted and the rest 64.29% were kept aphakic [Figure 4] as the majority of our study population were under 2 years. Shah et al.[18] conducted a study where 67.6% of patients were kept aphakic.
Figure 3: Distribution of the total number of eyes operated in 21 patients

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Figure 4: Distribution of immediate postoperative complications among the pseudophakic and aphakic groups (n = 28)

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Some immediate postoperative complications were noted such as anterior uveitis (nine eyes), corneal edema (three eyes), and striate keratitis (six eyes), and the rest had no significant complications. However, most of them were more prevalent in the aphakic group [Figure 4]. Jyoti et al.[1] found transient corneal edema (four eyes), capsule phimosis (two eyes), and fibrinous uveitis (four eyes) as significant postoperative complications. Various studies such as Shah et al.[18] also pointed that aphakic patients were more prone to immediate and delayed postoperative complications.

At the final visit, significant improvement of best-corrected visual acuity (≥6/60) was noted in 52.38% of eyes against 5.12% preoperative with P < 0.01 [Table 4]. On the contrary, lesser number of eyes (38%) had best-corrected visual acuity < 6/60 than preoperative which was 95% with “P” < 0.05 [Table 4]. However, in the retrospective study by Vijayalakshmi et al.,[11] visual acuity at a duration of 68.5 months was ≥6/24 in 15% of eyes and 55% of eyes had visual acuity ≤3/60. The long-term complications of surgery were probably responsible for this variation from our study.
Table 4: Comparison between pr-. and postoperative best-corrected visual acuity

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High clinical surveillance of signs and symptoms of CRS patients should be carried out. Furthermore, following cataract surgery, the visual outcomes and complications should be properly monitored in CRS. Irrespective of quality eye care services (with or without intraocular lens implantation) given to the CRS patients It will continue to be remain poor because of long follow up schedules, increased prevalence of visual, auditory, and neurological complications.

However, ocular consequences of CRS are not limited to abnormalities noted in the neonatal period.[19] It may be a drawback of our study as we limited our study period up to 6 months following surgery. Further to add to limitation, there was no control group for comparison and also small sample size diminished the power of the study. IgG antibodies in newborns may be derived from mothers and can be detected for up to 6 months. In this study, serology for TORCH was not carried out in the mothers, thus the clinical significance of the presence of IgG antibodies could not be documented properly. Therefore, pregnant women should also be screened so that they can be vaccinated after delivery. Male preponderance on the study population may not necessarily indicate the actual increased prevalence of rubella cataracts among them. It may be an indication of gender bias in India as male children are given more priority than females.

Noteworthy improvement in visual outcome was noted with early diagnosis and treatment with acceptable rate of immediate postoperative complications. We must emphasize immunization of children, identification of vaccine failures, and immunization of susceptible women before their pregnancy.

Ethical clearance

I.P.G.M.E and R Research oversight Committee with Reference no. IPGME&R/IEC/2020/002 dated 07.01.2022.


  Conclusion Top


Noteworthy improvement in visual outcome was noted with early diagnosis and intervention with acceptable rate of immediate postoperative complications.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Jyoti M, Shirke S, Matalia H. Congenital rubella syndrome: Global issue. J Cataract Refract Surg 2015;41:1127.  Back to cited text no. 1
    
2.
Merdassi A, Limaiem R, Turki F, Chaker N, Falfoul Y, Mghaieth F, et al. Ophthalmologic manifestations of congenital rubella. Arch Pediatr 2011;18:870-3.  Back to cited text no. 2
    
3.
Robertson SE, Featherstone DA, Gacic-Dobo M, Hersh BS. Rubella and congenital rubella syndrome: Global update. Rev Panam Salud Publica 2003;14:306-15.  Back to cited text no. 3
    
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Duszak RS. Congenital rubella syndrome – Major review. Optometry 2009;80:36-43.  Back to cited text no. 4
    
5.
Malathi J, Therese KL, Madhavan HN. The association of rubella virus in congenital cataract – A hospital-based study in India. J Clin Virol 2001;23:25-9.  Back to cited text no. 5
    
6.
Eckstein M, Vijayalakshmi P, Killedar M, Gilbert C, Foster A. Aetiology of childhood cataract in south India. Br J Ophthalmol 1996;80:628-32.  Back to cited text no. 6
    
7.
Mahalakshmi B, Therese KL, Devipriya U, Pushpalatha V, Margarita S, Madhavan HN. Infectious aetiology of congenital cataract based on TORCHES screening in a tertiary eye hospital in Chennai, Tamil Nadu, India. Indian J Med Res 2010;131:559-64.  Back to cited text no. 7
[PUBMED]  [Full text]  
8.
Lahbil D, Souldi L, Rais L, Lamari H, El Kettani A, Zaghloul K. Les manifestations ophtalmologiques de la rubéole congénitale: aspects cliniques et épidémiologiques [Manifestation of congenital rubella syndrome: Clinical and epidemiologic aspects]. Bull Soc Belge Ophtalmol 2007;(303):13-20. French.  Back to cited text no. 8
    
9.
Masresha B, Shibeshi M, Kaiser R, Luce R, Katsande R, Mihigo R. Congenital rubella syndrome in the African region - Data from sentinel surveillance. J Immunol Sci 2018;Suppl:146-150.  Back to cited text no. 9
    
10.
Murhekar M, Verma S, Singh K, Bavdekar A, Benakappa N, Santhanam S, et al. Epidemiology of Congenital Rubella Syndrome (CRS) in India, 2016-18, based on data from sentinel surveillance. PLoS Negl Trop Dis 2020;14:e0007982.  Back to cited text no. 10
    
11.
Vijayalakshmi P, Srivastava KK, Poornima B, Nirmalan P. Visual outcome of cataract surgery in children with congenital rubella syndrome. J AAPOS 2003;7:91-5.  Back to cited text no. 11
    
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Leung AK, Hon KL, Leong KF. Rubella (German measles) revisited. Hong Kong Med J 2019;25:134-41.  Back to cited text no. 12
    
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Désinor OY, Ansèlme RJ, Laender F, Saint-Louis C, Bien-Aimé JE. Seroprevalence of antibodies against rubella virus in pregnant women in Haiti. Rev Panam Salud Publica 2004;15:147-50.  Back to cited text no. 13
    
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Cutts FT, Robertson SE, Diaz-Ortega JL, Samuel R. Control of rubella and Congenital Rubella Syndrome (CRS) in developing countries, Part 1: Burden of disease from CRS. Bull World Health Organ 1997;75:55-68.  Back to cited text no. 14
    
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Best JM. Rubella. Semin Fetal Neonatal Med 2007;12:182-92. Epub 2007 Mar 2.  Back to cited text no. 15
    
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Dewan P, Gupta P. Burden of Congenital Rubella Syndrome (CRS) in India: A systematic review. Indian Pediatr 2012;49:377-99.  Back to cited text no. 16
    
17.
Singh MP, Ram J, Kumar A, Khurana J, Marbaniang M, Ratho RK. Infectious agents in congenital cataract in a tertiary care referral center in North India. Diagn Microbiol Infect Dis 2016;85:477-81.  Back to cited text no. 17
    
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Shah SK, Praveen MR, Vasavada AR, Vasavada VA, Carelli R, Trivedi RH, et al. Long-term longitudinal assessment of postoperative outcomes after congenital cataract surgery in children with congenital rubella syndrome. J Cataract Refract Surg 2014;40:2091-8.  Back to cited text no. 18
    
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Boger WP 3rd. Late ocular complications in congenital rubella syndrome. Ophthalmology 1980;87:1244-52.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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