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Trends over time in the incidence of congenital anophthalmia, microphthalmia and orbital malformation in England: database study
  1. Aruna Dharmasena1,2,
  2. Tiarnan Keenan1,
  3. Raph Goldacre3,
  4. Nick Hall3,
  5. Michael J Goldacre3
  1. 1Department of Oculoplastics, Lacrimal and Orbital surgery, Manchester Royal Eye Hospital, Manchester, UK
  2. 2Department of Adnexal surgery, Moorfields Eye Hospital, London, UK
  3. 3Unit of Health-Care Epidemiology, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  1. Correspondence to Aruna Dharmasena, Adnexal Service, Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, UK; aruna_dharmasena{at}


Aims To study trends over time in the incidence of congenital anophthalmia, microphthalmia and orbital malformations in England, along with changes in hospital admission rates for these conditions.

Methods Using English National Hospital Episode Statistics (1999–2011), the annual rate of hospital admissions related to anophthalmia, microphthalmia and congenital malformations of orbit/lacrimal apparatus was calculated per 100 000 infants. The records were person-linked, which enabled patients' ‘first record’ rates to be calculated as proxies for incidence. Similar analyses on pre-1999 datasets were also undertaken for microphthalmia.

Results There was no systematic increase or decrease over time in the incidence of these conditions, but there was some fluctuation from year to year. The incidence of congenital anophthalmia ranged from 2.4 (95% CI 1.3 to 4.0) per 100 000 infants in 1999 to 0.4 (0 to 1.3) in 2011. The annual incidence of congenital microphthalmia was 10.8 (8.2 to 13.5) in 1999 and 10.0 (7.6 to 12.4) in 2011. The annual incidence of congenital orbital/lacrimal malformations was 0.5 (0 to 1.1) in 1999 and 0.7 (0 to 1.4) in 2011. Including multiple admissions per person, admission rates for microphthalmia showed a linear increase over time from 1999. The earlier data for microphthalmia indicated an increase in admission rates, but no change in incidence, from 1971 to 2011.

Conclusions The incidence of these conditions has remained stable in England in recent years. Although the incidence of microphthalmia was stable, hospital admission rates for it increased over time reflecting an increase in multiple admissions per affected person. These data may be useful for planning service provision.

  • Embryology and development
  • Epidemiology
  • Genetics
  • Lacrimal drainage

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Anophthalmia and microphthalmia are rare congenital conditions defined, respectively, by the absence of an eye or the presence of a small, poorly developed eye within the orbit. Together with congenital malformations of the orbit and ocular adnexa, these conditions may present substantial challenges to the ophthalmologist and orbital surgeon, and a significant treatment burden to the patient and family.

Anophthalmia and microphthalmia are thought to represent a phenotypic spectrum.1 ,2 While their exact pathogenesis is not fully understood, genetic causes can include chromosomal abnormalities (together with some monogenic and polygenic variants), while environmental factors such as intrauterine infections or toxins may also be involved.2 These factors lead to abnormal differentiation of the neuroectodermal tissues required for ocular and adnexal development, such that one or both eyes fail to develop normally, with a variable degree of abnormalities ranging from microphthalmia to ‘true anophthalmia’.1 ,2 In one-third of cases, the ocular pathology is associated with a systemic syndrome.2

Individuals with these conditions usually have a high degree of visual impairment, including bilateral blindness in some cases; together with the altered physical appearance, this may have substantial implications on the social and psychological welfare of the child and family.3 Since normal facial development is highly dependent on orbital growth, the timely management of severe microphthalmic and anophthalmic orbits is fundamental in preventing gross facial disfigurement. Serial conformers and socket expanders are often required in these individuals, but additional measures may be required in some cases, particularly in the presence of associated eyelid abnormalities. In general, affected individuals will require multiple hospital admissions and operations over many years, and will likely remain under the care of the oculoplastic surgeon, orbital surgeon and ocularist for much of their life.

While anecdotal reports have suggested that hospital admissions related to ocular and adnexal malformations have been increasing in England in recent years, we are not aware of any published literature in this area. We have therefore used linked English National Hospital Episode Statistics (HES) to analyse annual hospital admission rates for anophthalmia, microphthalmia and congenital malformations of the orbit/adnexa.


Since 1999, every day-case and inpatient admission in English National Health Service (NHS) hospitals has been recorded, as a statistical summary of the case, in HES with the means for successive records for the same person to be linked together. A day-case, in the English NHS, is a planned hospital admission in which the patient is not intended to stay overnight. Records of babies born in hospital, as well as records of day-case and inpatient care, were included in the study to capture diagnoses made in infants when still in hospital after birth and who were, technically, not ‘admissions’. In this study, we analysed linked HES statistics for England relating to anophthalmia, microphthalmia and congenital malformations of orbit/agenesis of lacrimal apparatus. The HES data were provided by the English National Health and Social Care Information Centre (HSCIC). HSCIC was unable to provide data from 2012 onwards. Records of day-case care and inpatient admissions were identified for these congenital malformations using the codes of the International Classification of Diseases (ICD). The codes used for anophthalmia were Q11.0–Q11.1 in ICD-10. The code used for microphthalmia was Q11.2 in ICD-10. Those used for congenital malformations of orbit and agenesis of lacrimal apparatus were Q10.7 and Q10.4 in ICD-10.

The HSCIC data provided to our research team included encrypted values of unique identifiers for each individual on each HES record: these were based on the NHS number (unique to each person registered for NHS care) and the HES Identification Number (unique to each person using NHS hospital care). Record linkage was used to determine the incidence, as closely as possible, of the malformations. Record linkage means that the anonymised records for each individual can be traced over time through multiple admissions, such that one can distinguish numbers of admissions from numbers of separate individuals being admitted. Linkage of England HES data only became possible from 1999. Using the record-linked dataset, two annual rates were generated as follows. The episode-based rate includes all episodes of admission, regardless of how many admissions an individual has (the ‘hospital admission rate’); the person-based ‘first record’ rate counts each person once, and once only, and allocates the person to the year in which the first-recorded admission occurred (the ‘incidence rate’). English national population denominators were obtained from the Office for National Statistics for each calendar year. The analyses were confined to children less than 1 year of age to approximate the birth incidence of the malformations.

For microphthalmia, we used three other datasets that included data prior to 1999. The first was an unlinked all-England hospital dataset of HES spanning 1990–1998; the second, an unlinked all-England 1-in-10 sample of hospital admissions (the Hospital In-Patient Enquiry, HIPE) spanning 1971–1985; the third, a dataset for the former Oxford NHS Region, the Oxford Record Linkage Study (ORLS), which is like HES but was fully linked spanning 1971–2011. The code used for microphthalmia prior to 1995 was 743.1 in ICD-9. The number of cases of anophthalmia was too small to justify analysis in HIPE and the ORLS; and separate codes for congenital orbital malformations were not available in these earlier data.


Congenital anophthalmia

Incidence rates

The annual incidence of anophthalmia fluctuated from year to year, with no overall rise or fall (figure 1). The lowest recorded annual incidence was 0.4 (95% CI 0.0 to 1.3) per 100 000 infants, based on three infants out of a total of 679 100 infants in 2011. The highest recorded annual incidence was 2.4 (1.3 to 4.0), based on 14 infants out of 592 200 in 1999. The data did demonstrate some significant differences in incidence rates between years: for example, the rate of 2.4 per 100 000 infants in 1999 was outside the upper 95% CI of 1.3 in 2011, see above.

Figure 1

The incidence of congenital anophthalmia and annual incidence of congenital anophthalmia-related hospital admissions in England (1999–2011). HES, Hospital Episode Statistics.

Considered as rates grouped in the two most recent quinquennia of years of occurrence, to bolster statistical power, the annual rates for both sexes combined in 2002–2006 and 2007–2011 were, respectively, 1.5 (1.0 to 1.9) and 1.4 (1.0 to 1.8) per 100 000 infants. The corresponding rates for females were 1.4 (0.8 to 2.0) and 1.0 (0.5 to 1.5). Those for males were 1.6 (1.0 to 2.2) and 1.8 (1.2 to 2.5).

Hospital admission rates

Similar findings were observed over time for hospital admission rates (figure 1), that is, annual fluctuations but no overall increase or decrease over time. The grouped rates for both sexes combined in 2002–2006 and 2007–2011, respectively, were 5.0 (3.9 to 6.1) and 4.1 (3.1 to 5.1).

Congenital microphthalmia

Incidence rates

The annual incidence of microphthalmia was substantially higher than that for anophthalmia, for example, 10.0 versus 0.4 per 100 000 infants in 2011. The incidence of microphthalmia was stable at 10.8 (8.2 to 13.5) per 100 000 infants in 1999 and 10.0 (7.6 to 12.4) in 2011 (figure 2). Male rates (9.6, 8.2 to 11.1 in 2007–2011) and female rates (9.7, 8.2 to 11.3) were very similar.

Figure 2

The incidence of congenital microphthalmia and annual incidence of microphthalmia-related hospital admissions in England (1999–2011). HES, Hospital Episode Statistics.

Hospital admission rates

Annual admission rates for microphthalmia showed a linear increase over time from 1999 to 2011 (figure 2) with an annual change of 3.2% (95% CI 0.8% to 5.7%), that is, there was a divergence between incidence and admission rates, attributable to a significant increase in multiple admissions per person with microphthalmia.

Rates from 1971

Using the longer runs of data, for England and from the ORLS, it is clear that hospital admission rates had also been increasing prior to 1999 (table 1). In the all-England dataset they increased from 3.2 (1.4 to 5.0) in 1971–1975 to 10.6 (9.6 to 11.6) in 1991–1996, and then to 18.7 (17.2 to 20.2) in 2007–2011. Data from the ORLS also show an increase, though a little later in time (table 1). The person-based incidence data in the ORLS show that the increases in admission rates did not reflect an increase in incidence rates. The increase in admission rates represents an increase in multiple admissions per person (table 1).

Table 1

Hospital admission rates and incidence rates* for microphthalmia, with 95% CIs, England and the Oxford Record Linkage Study (ORLS) area, 1971–2011

Congenital malformation of orbit/agenesis of lacrimal apparatus

Incidence rates

There was no significant increase in annual incidence rates. The rates were 0.5 (0.0 to 1.1) per 100 000 infants in 1999 and 0.7 (0.1 to 1.4) in 2011 (figure 3). Grouped into quinquennia, rates were 0.4 (0.2 to 0.6) in 2002–2006 and 0.8 (0.5 to 1.1) in 2007–2011. Differences between males and females were not significant: for example, in the last 5 years of the study they were 0.9 (0.4 to 1.3) in males and 0.6 (0.2 to 1.0) in females.

Figure 3

The incidence of congenital malformations of orbit and agenesis of lacrimal apparatus and the incidence of hospital admissions related to these congenital anomalies in England (1999–2011). HES, Hospital Episode Statistics.

Hospital admission rates

Annual rates of hospital admissions were 0.6 (0.3 to 0.9) in 2002–2006 and 1.2 (0.8 to 1.6) in 2001–2011.


Congenital anophthalmia and microphthalmia are rare but severe conditions, where each affected individual will require extensive care from ophthalmology and orbital services over many years, together with social and psychological support.

Our results show that the incidence of anophthalmia has remained stable in England over the past decade. The mean annual incidence of 1.5 cases per 100 000 infants represents an average of about nine infants newly diagnosed per year. The annual incidence of microphthalmia has been much higher, at an average of 8.6 cases per 100 000 infants (representing around 53 infants newly diagnosed per year). The incidence of congenital orbital/lacrimal malformations is much lower, with an annual rate of 0.5 cases per 100 000 infants (representing three infants newly diagnosed each year).

Potential factors affecting the incidence of these congenital conditions include both genetic and environmental factors.1 ,2 Genetic factors include chromosomal abnormalities (such as duplications, deletions and translocations, eg, duplication 3q syndrome), monogenic causes (particularly in SOX2) and polygenic variants (in genes including PAX6, OTX2 and CHX10).2 Potential environmental factors include gestational infections (eg, rubella and toxoplasmosis), vitamin A deficiency and other exposures (eg, fever, hyperthermia, X-rays and toxic drugs such as alcohol and warfarin).2 Because of the complex balance of potential causative factors, it is difficult to know exactly why incidence rates for anophthalmia and microphthalmia have been stable in the years covered by this study. One would assume that the incidence of congenital infections and other toxic insults has been decreasing in England in recent years.4 ,5 However, these factors might potentially be balanced by other effects such as improved care and survival for children with major systemic abnormalities (ie, those associated with anophthalmia/microphthalmia) and changes in the prevalence of genetic disorders (eg, through altered rates of consanguinity). Other factors potentially affecting the measured incidence may include increased rates of prenatal diagnosis leading to termination of pregnancy, decreased threshold for hospital admission (eg, for imaging studies or surgical treatment) and changes in accuracy of diagnosis and coding (eg, better discrimination between microphthalmia and anophthalmia).

The increase in the annual number and rate of hospital admissions for microphthalmia, with an unchanging background rate of incidence, is likely to be explained by an increased understanding of the fact that steady growth of the orbit is crucial for development of the mid-face. This is usually achieved by techniques including serial insertion of custom-made confirmers and injection of orbital expanders. Together with ocular and orbital imaging procedures, these interventions may require general anaesthesia and day-case or inpatient admissions. These data are useful in the planning of services for the future, particularly in specialist centres where much of this work is undertaken.

Previous studies

There is a paucity of epidemiologic information on severe congenital malformations of the eye, orbit and ocular adnexa. Epidemiologic studies of this kind are difficult to conduct because of the rarity of these conditions and, to the best of our knowledge, there are no studies examining time trends in the English population over the past two decades. Previous published studies have generally used data extracted from national congenital anomaly registers.6–9 In previous studies carried out on predominantly Caucasian populations, the incidence of anophthalmia has been reported between 0.6 and 6 cases per 100 000 births,6 ,10–16 while that of microphthalmia has reportedly ranged from 5.5 to 17.0 per 100 000 births.6 ,10–16 Our incidence figures sit within these ranges.

The study most comparable to ours was undertaken by the Surveillance of Eye Anomalies UK Special Interest Group over a period of 18 months, from October 2006, throughout the UK.6 For anophthalmia, the incidence figure reported in this study was 0.6 (0.3 to 1.3) per 100 000, based on seven cases reported over the 18-month study period,6 equivalent to fewer than five cases per year. By comparison, the incidence rates in our study during the calendar years 2006, 2007 and 2008 were more than twice that, despite our study being limited to England only. The equivalent numbers of cases captured in our study for England only during the calendar years 2006, 2007 and 2008 were 13, 8 and 15, respectively.

The same investigators reported an incidence for microphthalmia (isolated and colobomatous) of 5.5 (3.8 to 7.8) per 100,000, based on 63 cases reported over the 18-month study, equivalent to 42 cases per year.6 By comparison, the incidence figures in our study during the calendar years 2006, 2007 and 2008 were 8.0, 7.6 and 9.3 cases per 100 000, respectively, that is, somewhat higher in our study, again despite our study being limited to England only. The equivalent numbers of cases captured in our study during the calendar years 2006, 2007 and 2008 were 49, 49 and 62, respectively.

These discrepancies may perhaps be explained partly by under-reporting of relevant cases to the British Ophthalmic Surveillance Unit in the previous study.6 though we cannot exclude the possibility of over-ascertainment in our study through inaccurate diagnosis or coding. In particular, we cannot exclude the possibility that some cases of microphthalmia could have been coded incorrectly as anophthalmia (hence leading to increased numbers in our study), especially since these conditions are thought to exist on a spectrum.

We are not aware of any previous studies examining the incidence of congenital abnormalities of the orbit or agenesis of the lacrimal system.

Strengths and weaknesses

The main strengths of this study include the use of a dataset that covers the whole of the English NHS population over a long time span. Linkage in the dataset means that we have been able to distinguish between number of hospital admissions and number of separate infants being admitted. We have, therefore, provided incidence rates of these congenital anomalies as well as rates of hospital admissions. It is likely that every case of these congenital anomalies will have been recorded in hospital statistical data, either because the baby was born in hospital or because, if not born in hospital, is likely to have been admitted after birth. Our findings are consistent with those from studies conducted in other European countries. However, potential weaknesses in the dataset include lack of evidence about the accuracy of diagnostic coding and the exclusion of admissions to hospitals in the private sector; privacy regulations in England preclude access to original case records in studies like ours. In addition, data capture in this study is dependent on hospital admission. This means that individuals will not be captured in cases where no hospital admission occurs for imaging, surgery or medical reasons, for example, mild microphthalmia where no orbital imaging or surgical intervention takes place.

In conclusion, our results show that the incidence of these conditions has remained stable in England over the past decade. The incidence is higher than previous UK estimates but at the lower end of the range reported previously for various European countries. Hospital admission rates for microphthalmia have increased, representing an increase in the number of multiple admissions per child (eg, for imaging and surgical procedures). These data may provide insights into potential causative factors; for example, incidence rates for these congenital abnormalities are not decreasing despite declining rates of congenital infections and other improvements in antenatal care. This information is also helpful for planning service provision in this area, as children with anophthlamia/microphthalmia require extensive care from ophthalmology and orbital departments over many years.


Record linkage was undertaken on the English national dataset by the Oxford Record Linkage Study team.



  • Contributors AD had the idea for the paper. NH and MJG were responsible for the data acquisition. MJG designed the analyses. NH and RG analysed the data. All authors interpreted the data, and wrote and revised the paper. MJG is the guarantor.

  • Funding The Unit of Health-Care Epidemiology was funded by the English National Institute for Health Research to build the linked dataset for multiple purposes. RG's salary is part-funded by Public Health England.

  • Competing interests None declared.

  • Ethics approval Ethical approval for analysis of the record linkage study data was obtained from the Central and South Bristol Multi-Centre Research Ethics Committee.

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