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Clinical spectrum of non-syndromic microphthalmos, anophthalmos and coloboma in the paediatric population: a multicentric study from North India
  1. Shailja Tibrewal,
  2. Ketaki Subhedar,
  3. Pradnya Sen,
  4. Amit Mohan,
  5. Shivanand Singh,
  6. Chintan Shah,
  7. Ken K Nischal,
  8. Suma Ganesh,
  9. The Bodhya Eye Consortium
  1. Correspondence to Ken K Nischal, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA; nischalkk{at}


Aims To describe the clinical features, visual acuity and causes of ocular morbidity in children (0–18 years) with microphthalmos, anophthalmos, and coloboma (MAC) from North India.

Methods A retrospective study conducted between October 2017 and September 2018 in three tertiary eye institutes, part of the Bodhya Eye Consortium with consensus led common pro formas. Children with complete clinical data and without syndromic/systemic involvement were included. The clinical phenotype was divided into isolated ocular coloboma (CB), coloboma with microcornea (CBMC), colobomatous microphthalmos (CBMO), non-colobomatous microphthalmos (MO) and anophthalmos (AO).

Results A total of 532 children with MAC were examined. Seventeen records were excluded due to incomplete data (0.2%). 515 children (845 eyes) were included: 54.4% males and 45.6% females. MAC was unilateral in 36% and bilateral in 64%. CB, CBMC, CBMO, MO and AO were seen in 26.4%, 31%, 22%, 8% and 12.5% of eyes, respectively. Nystagmus was found in 40%, strabismus in 23%, cataract in 18.7% and retinal detachment in 15%. Best-corrected visual acuity (BCVA) of <3/60 was seen in 62.4% eyes. Blindness (BCVA <3/60 in better eye) was seen in 42.8% of bilateral patients. Those with microcornea or microphthalmos with coloboma had worse BCVA (p<0.001). There were regional differences in the type of MAC phenotype presenting to the three institutes.

Conclusion The MAC group of disorders cause significant ocular morbidity. The presence of microcornea or microphthalmos with coloboma predicts worse BCVA. The variation of the MAC phenotype with the district of origin of the patient raises questions of aetiology and is subject to further studies.

  • Choroid
  • Embryology and development
  • Eye (Globe)
  • Iris
  • Retina

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Microphthalmos, anophthalmos and coloboma (MAC) are a group of structurally and clinically related congenital ocular malformations with a wide spectrum of manifestations.1 2 Anophthalmos (AO) refers to the complete absence of ocular tissues on clinical examination. Microphthalmos is when the eye is small by at least two SD of the normal and may be complex or simple depending on the presence or absence of additional ocular structural abnormalities. Coloboma results from the incomplete closure of the optic fissure, which may be associated with microphthalmos or orbitopalpebral cysts.2

There is considerable genetic and phenotypic heterogeneity between all three entities. Although the genetic basis of the MAC group of disorders is still poorly understood, most of the genes identified so far involve those that regulate cell proliferation, migration and differentiation into various compartments and apoptosis.3–5 Environmental insults during fetal development have also been postulated but not proven to cause congenital eye malformations.6 7 Studies have shown that MAC may present as varying combinations between the two eyes of the same person or between different members of the same pedigree.8–11 The MAC complex of disorders may be considered a spectrum of conditions with anopthalmos being the most severe and isolated iris coloboma the milder end.

MAC is a significant cause of ocular morbidity and childhood blindness in India.12–17 The proportion of childhood blindness attributed to MAC varies from 20% in population surveys to 25–55% in various blind school surveys in India.12–17 Studies in various parts of India have shown that the proportion of childhood blindness attributed to MAC is increasing with time.18–20 The visual acuity (VA) in coloboma and microphthalmos depends on the extent of retinal involvement and globe malformation, respectively. The other causes of reduced vision include the development of cataract, secondary glaucoma, retinal detachment (RD) and/or phthisis. Although there are few studies from India that describe the clinical features and reasons for poor vision and ocular morbidity in coloboma in children,21 22 there are none, to the best of our knowledge, describing the full array of clinical features of the MAC complex of disorders in children. We describe these disorders in a large sample of children from three tertiary eye-care centres in India.


This retrospective cross-sectional study was conducted over 1 year (October 2017– September 2018) in three tertiary eye-care institutes in India from three neighbouring states: Dr. Shroff’s Charity Eye Hospital (SCEH, New Delhi, Delhi), Sadguru Netra Chikitsalaya (SNC, Chitrakoot, Madhya Pradesh) and Sitapur Eye Hospital (SEH, Sitapur, Uttar Pradesh). These three eye-care centres are part of the Bodhya Eye Consortium, which includes five eye-care centres (SCEH, New Delhi; SNC, Chitrakoot; SEH, Sitapur; Aditya Jyot Eye Hospital, Mumbai, Maharashtra; Akhand Jyot Eye Hospital, Patna, Bihar). Only three centres participated in this study since they had medical staff available to partake in this study at the time it was initiated. The purpose of the eye consortium is to allow the development of evidence-based consensus led protocols and studies to provide consistent and robust big data from both urban and non-urban eye-care centres in North India.

Institutional review board approval was obtained at each of the three participating centres. Agreed protocols for collection of data were developed and the same pro forma was used at each of the three sites to collect data. Medical records of all the children with MAC aged below 18 years were de-identified and included.

The following data were recorded: age at presentation, gender, address, birth history, family history, laterality of the condition, uncorrected distance VA, refraction, best-corrected visual acuity (BCVA) for distance, strabismus, extraocular motility, nystagmus, microcornea, coloboma, cataract, lens coloboma, glaucoma, RD, microphthalmos, AO or phthisis. The extent of the coloboma was noted in terms of involvement of the iris, retina, macula and/or disc. Additional adnexal, corneal or retinal findings were noted. The findings of posterior segment ultrasonography if performed were recorded, especially in those patients with media opacities. The findings of AO, microphthalmos and microcornea were based on clinical evaluation. Measurement of the corneal size or axial length was not performed in all patients. Radiological, ultrasonographic or histological confirmation of true AO was not performed. Thus, anophthalmos was defined as ‘no visible sign of globe’, and microphthalmos was defined as ‘visibly small eyes’. Isolated ocular coloboma (CB) was defined as coloboma without microcornea or microphthalmos. The phenotype was then classified as CB, coloboma with microcornea (CBMC), colobomatous microphthalmos (CBMO), non-colobomatous microphthalmos (MO) and clinical AO.

The VA was recorded using age-appropriate vision tests. In children, unable to see 20/200 on the vision chart, acuity was recorded by either moving them closer to the chart or by assessing the ability to count fingers, detect hand movements, light perception or no-light perception. VA was converted to Logarithm of the Minimum Angle of Resolution (LogMAR) using standard tables to enable statistical analysis. Hand movement vision was converted to a LogMAR value of 3. The presence or absence of perception of light was considered as mere detection of stimulus, hence not converted to LogMAR and analysed separately.23 VAs were classified according to WHO categories. Children were considered to have blindness if the BCVA in the better-seeing eye was <3/60. Since there is no congenital defect registry in our country, the possibility of duplication of patients in the various centres was contemplated. Thus, patients with a similar demographic profile (ie, name, age and gender) in the three institutes data set were compared in terms of clinical findings and final diagnosis. We did not find any such duplication among the patients presenting during the study period. The proportion of children with MAC presenting to each centre was calculated by dividing the number of children with MAC from the total number of children (0–18 years) visiting each centre during the study period.

Those patients with incomplete records and ambiguous diagnosis were excluded. Children with documented dysmorphism, syndromes or systemic illnesses were also excluded.

The data were compiled in Excel, and analysis was performed at one of the centres (SCEH). Descriptive statistics included calculation of numbers, percentages, mean and range. χ2 Test or Fischer’s exact test was used to evaluate the difference in BCVA between the various phenotypes of MAC and the differences in phenotypic categories of MAC among the three institutes. A p value of less than 0.05 was considered statistically significant.


A total of 532 children with non-syndromic MAC were examined in the three participating centres during the study period. Seventeen records were excluded due to incomplete data (0.2%). Thus, 515 children (845 eyes) were included. There were 280 males (54.4%) and 235 females (45.6%), p=0.005. A total of 330 children (64%) had bilateral and 185 (36%) had unilateral involvement. Among the unilateral patients, the right eye was involved in 85 (45.9%) and left eye in 100 (54.1%) patients (p=0.115). The average age at presentation was 7.9±6 years in bilateral and 9.4±5.8 years in unilateral patients (p=0.006). The most common presenting symptoms were reduced vision or a ‘small eye’ with inability to open eyes since birth, shaking of the eyes since birth and watering of the eyes also being reported. Birth and developmental history were not recorded in 133 children, in the remainder (382), low birthweight was seen in 4 children (1%), twin pregnancy in 2 (0.5%), prematurity in 4 (1%), maternal anaemia, antepartum haemorrhage and delayed crying in 1 each. Among the unilateral patients, no other family member was affected. Five children with bilateral MAC had one other family member affected (1.5%). Consanguinity was present in 12 patients (2.3%).

Spectrum of MAC in the study patients

AO was seen in 106 eyes (12.5%), MO in 68 eyes (8%), CBMO in 186 eyes (22%), CBMC in 262 eyes (31%) and CB in 223 eyes (26.4%). Six anophthalmic eyes had a cystic mass replacing the globe. Microcornea was seen in 425 eyes (50.3%). This included CBMC in 262 eyes, CBMO in 136 eyes and MO in 27 eyes. Figure 1A shows the distribution of these phenotypes among the unilateral, bilateral and total eyes. The phenotype in both eyes tended to be similar in 264 (80%) patients with bilateral affection. Combinations of different phenotypes in each eye were seen in 66 (20%) patients. Figure 1B and C shows the various combinations of phenotypes seen in bilateral patients.

Figure 1

(A) Distribution of the MAC phenotype among the unilateral, bilateral and total eyes (n=845). (B) Distribution of similar MAC phenotypes (n=264) in the two eyes of patients with bilateral MAC. (C) Distribution of dissimilar phenotypes (n=66) seen in the two eyes of patients with bilateral MAC. Numbers on the y-axis indicate the number of eyes. AO, anophthalmos with or without cyst; CB, isolated ocular coloboma; CBMC, coloboma with microcornea; CBMO, colobomatous microphthalmos; MAC, microphthalmos, anophthalmos and coloboma; MO, non-colobomatous microphthalmos.

Extent of coloboma

Coloboma was seen in 671 eyes (79.4%). This included 149 (80.5%) unilateral and 261 (79.1%) bilateral patients. It was associated with microcornea in 39% of eyes, microphthalmos in 27.8% of eyes and the rest were isolated. Data regarding the extent of coloboma were missing in two patients with unilateral and three patients with bilateral involvement due to either media opacities or RD obscuring the view (0.9%). Figure 2A shows the extent of coloboma in the 663 eyes with complete data. The extent of coloboma was similar between the unilateral and bilateral patients. Figure 2B shows the extent of retinal involvement among the 611 (91%) eyes with retinal coloboma.

Figure 2

(A) Extent of involvement of the various parts of eye by the coloboma in 663 eyes and (B) extent of retinal involvement in terms of macula and disc spared or included in the coloboma among 611 eyes.

Comorbid conditions

These results apply to 739 eyes, excluding the 106 with AO. Table 1 shows the distribution of the associated major comorbidities and complications among the patients. Apart from coloboma, the other anterior segment findings were band keratopathy (8 eyes; 1%), unspecified corneal scarring (9 eyes; 1%), sclerocornea (10 eyes; 1%), anterior segment dysgenesis (1 eye), aniridia (1 eye) and megalocornea (1 eye). Apart from RD, other retinal findings were retinal pigment epithelial mottling at fovea (4 eyes; 0.5%), macular scar (1 eye), foveal hypoplasia (1 eye) staphyloma (9 eyes; 1%), subretinal haemorrhage (2 eyes), lattice degeneration (3 eyes), pigmentary retinopathy (1 eye), spontaneously attached retina (2 eyes) and intercalary membrane detachment (7 eyes; 0.9%). Optic disc abnormalities other than coloboma were optic disc pit (1 eye), hypoplasia (3 eyes), tilted disc (1 eye) and hyperaemic crowded disc (4 eyes; 0.5%).

Table 1

Comorbid conditions associated with MAC

Visual acuity

Data for VA were present for 712 eyes (84.3%). In 56 eyes, VA was not recorded. There were 77 eyes where vision was recorded as only fixing and following light in young children and hence could not be included in analysis. Table 2 shows the distribution of the BCVA in the 712 eyes according to the phenotype of the MAC disorder. Anophthalmic eyes had no-light perception. Overall, 446 eyes (62.6%) had BCVA less than 3/60. Among the eyes with coloboma and/or microphthalmos, 341 eyes (56.2%) had BCVA less than 3/60. The BCVA was poorer in colobomatous eyes with microphthalmos or microcornea than without them (p<0.001).

Table 2

Distribution of best-corrected visual acuity in eyes with MAC disorder*

Among the unilateral MAC, the other eye had a better vision in all except one patient. In this patient, the other eye had post-traumatic phthisis. One patient had blindness due to CBMO in one eye and optic atrophy in the contralateral eye. The proportion of patients with blindness and other categories of vision as per WHO criteria among bilateral MAC is shown in table 3. Blindness due to MAC was seen in 115 patients (42.8%) with bilateral MAC in whom VA data were available (n=269 patients). Almost three-fourth of the patients (195; 72.5%) had VA <6/18 in the better eye.

Table 3

WHO categories of visual impairment (BCVA in better eye) among the patients with bilateral MAC*

Refraction was possible in 85 eyes with unilateral MAC and 318 eyes with bilateral MAC. It was not possible in others due to conditions like media opacities, RD, AO or extreme microphthalmos. Correction of refractive errors, where possible, improved vision marginally. The average measurable VA improved from 6/95 to 6/65 with glasses.

Differences among the three institutes

The proportion of patients with MAC among all children aged below 18 years presenting to the participating institutes in the study period was 0.003% (98/32 562) in SCEH, Delhi; 0.017% (422/24 338) in SNC, Chitrakoot; and 0.016% (325/20 439) in SEH, Sitapur. The distribution of the MAC phenotype varied among the three institutes as shown in online supplementary material 1. Sixty-one per cent of eyes from SEH had severe phenotypes (CBMO, MO and AO) as compared with 35.8% from SCEH and 29.5% from SNC (p<0.001). The proportion of CB was however similar in all the three institutes. Some of the districts with several patients with MAC were Sitapur (117), Satna (44), Lakhimpur Kheri (35), Banda (25) and Chitrakoot (16). Online supplementary material 2 shows the district-wise distribution of the number of patients with MAC presenting to the three participating centres.


MAC disorders are congenital defects that contribute considerably to the number of disability years. The MAC spectrum of disorders affects a child’s quality of life similar to chronic systemic illnesses like acute lymphoblastic leukaemia.24 We studied the spectrum of MAC disorders and its comorbidities in a large sample of children from North India and analysed the regional clustering of these disorders among the three participating institutes. To the best of our knowledge, it is the largest multicentre study describing the clinical features of the MAC spectrum of disorders.

We found that among the MAC disorders, 79.4% of eyes had coloboma and 20.6% had MO or AO. The proportion of MAC involving coloboma varies in different populations ranging from 47% to 72.9%.1 25–27 The variations in the spectrum of these disorders may be due to different genetic constitutions of these populations. Hornby et al studied the proportion of blindness due to MAC in children in blind schools in 26 countries and found results varying from as low as 1.4% to as high as 33.2%.28 Among the unilateral eyes, we found the left eye to be more commonly affected as compared to that reported by Shah et al 1 who found the reverse. A similar phenotype was present in both eyes in 80% of our patients with bilateral MAC, similar to that seen by Shah et al. 1 Table 4 compares the spectrum of MAC disorders in the current study with available literature. The proportion of bilateral patients was higher in our study.

Table 4

Comparison of previous literature on clinical features of MAC with the current study

Colobomatous eyes had posterior segment involvement in 93.5%; higher than Shah et al’s1 report of 71.2%. Posterior segment colobomas were seen even in the absence of an iris coloboma in 5% of eyes emphasising the need for dilated funduscopy in all patients. The occurrence of microphthalmos or microcornea with coloboma in our study (27.7%, 50.3%) was greater than that reported by Uhumwangho and Jalali22 (19.1%, 45%) but less than Hornby et al 21 (36.7%, 79%). Hornby et al had conducted their study in children from blind schools which may account for this difference.

RD was seen in 15% of eyes, which is more than previously reported in the MAC spectrum.1 25 This could be attributed to the fact that the prior studies were performed in general hospitals as compared to our eye hospital-based study. Other clinic-based studies from the paediatric population report similar rates of RD in patients with chorioretinal colobomas (8.1%–17.6%).22 29 However, our rate was less than those studies where only chorioretinal colobomas and their complications have been analysed or have included adults as well30 31 but more than those with population-based samples.3235

Most of the prior MAC spectrum studies have not provided VA assessment data. It is difficult to quantitatively assess such low vision in children in the first few years of life. In our study, formal VA assessment could not be done in 15.7% of the eyes, but this is lower than previously reported (Shah et al,1 585%). Bilateral or severe sight impairment was noted in 44% of children in their study. Blindness (defined as BCVA <3/60 in the better eye) due to bilateral MAC in our study (42.8%) is comparable with the study by Hornby et al (39.5%).21 Our data also included anophthalmic eyes that would increase the proportion of blindness. The presence of microcornea and microphthalmos with coloboma predicted worse vision in both our study and that by Hornby et al. 21

While our results should be interpreted considering the retrospective design, the fact that we used consensus led pro formas to acquire data at three sites meant that our rate of exclusion of cases due to inadequate data was extremely low (0.2%). Although we excluded children with obvious syndromes, mild intellectual disabilities and undiagnosed systemic conditions might have been missed. Since axial length measurements and ultrasound examinations were not done in most patients, there could have been some overlap in the phenotypes of AO and extreme microphthalmos, and the diagnosis of posterior microphthalmos could have gone undetected. Some patients with normal axial length could have been labelled as microphthalmos in the presence of microcornea. Since examination under anaesthesia was not done for small children, there is a possibility that peripheral retinal colobomas may have been missed. Similarly, the assessment of microcornea was also based on clinical judgement. This could have underestimated the percentage of eyes with microcornea, especially in bilateral situations. These limitations have been found in previous studies as well.1 12 13 We could not determine the aetiological factors of the MAC spectrum due to lack of complete birth history, antenatal history and pedigree acquisition.

The fact that the rate of consanguinity in our study was 2.3% suggests that the information in this cohort is generalisable to countries with similar rates of consanguinity.33 While this is a strength, it may be considered a weakness because parts of Southern India have much higher rates of consanguinity and therefore a higher incidence of the MAC complex disorders.34 35

The strength of this study is the organised collaboration of three eye-care centres in North India which are part of the Bodhya Eye Consortium. Weekly teleconferences were used to develop and implement the pro formas well before the study period. This led to the acquisition of large data in a rare ocular disease, in a consistent and organised manner.

This study showed that improvement in vision after the refractive correction was often marginal. In unilateral cases, one child developed blindness because of trauma to the unaffected eye suggesting that the incidence of this event in this study in unilateral cases is 0.5%. This is an important figure to be able to give parents when counselling them about the use of polycarbonate protective glasses to safeguard the good eye. In developing countries, the cost of such glasses may be prohibitive.

To the best of our knowledge, this study is the largest of its kind and shows that the MAC spectrum of disorders causes considerable ocular morbidity. Nystagmus, cataract, strabismus and RD are the most common ocular comorbidities. We found that chorio-retinal and optic nerve colobomas were seen even in the absence of an iris coloboma in 5% of eyes and that the occurrence of RD was 15% when there was posterior segment involvement. The aetiology of the variation of the type of MAC complex disorder from the three regions served by the three eye-care centres is the subject of further studies.


We would like to acknowledge Mr Atanu Majumdar, Dr. Shroff’s Charity Eye Hospital, New Delhi, for help with statistical analysis. We would like to acknowledge all the members of the Bodhya Eye consortium (Dr. Shroff’s Charity Eye Hospital, New Delhi India; Sadguru Netra Chikitsalaya and Post Graduate Institute of Ophthalmology, Chitrakoot, Madhya Pradesh, India; Regional Institute of Ophthalmology and Sitapur Eye Hospital, Sitapur, Uttar Pradesh, India; Aditya Jyot Eye Hospital, Mumbai, Maharashtra, India; and Akhand Jyot Eye Hospital, Patna, Bihar, India) for supporting the research.



  • Twitter @nischalkk.

  • Contributors Conception and design: ST, SG. Analysis and interpretation: ST, KS, PS, AM, KKN, SG. Data collection: ST, KS, SS, CS. Critical review of manuscript: ST, KS, AM, PS, KKN, SG. Overall responsibility: ST, KS, PS, AM, SS, CS, KKN, SG.

  • Funding This work received partial funding from the World Society of Paediatric Ophthalmology and Strabismus (Registered 1144806, Charity Commission for England and Wales).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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