Abstract
Objectives
To determine the typical corneal changes in pure microphthalmia using a corneal topography system and identify characteristics that may assist in early diagnosis.
Methods
Patients with pure microphthalmia and healthy control subjects underwent corneal topography analysis (Orbscan IIZ® Corneal Topography System; Bausch and Lomb, Bridgewater, NJ, USA) to determine degree of corneal astigmatism (mean A), simulation of corneal astigmatism (sim A), mean keratometry (mean K), simulated keratometry (sim K), irregularities in the 3 - and 5-mm zone, and mean thickness of nine distinct corneal regions.
Results
Patients with pure microphthalmia (n = 12) had significantly higher mean K, sim K, mean A, sim A, 3.0 mm irregularity and 5.0 mm irregularity, and exhibited significantly more false keratoconus than controls (n = 12). There was a significant between-group difference in the morphology of the anterior corneal surface and the central curvature of the cornea.
Conclusions
Changes in corneal morphology observed in this study could be useful in borderline situations to confirm the diagnosis of pure microphthalmia.
Keywords
Introduction
Pure microphthalmia is a rare congenital abnormality in which the volume of the eyeball is much smaller than normal but there are no other significant eye malformations or systemic abnormalities. It is usually bilateral, and is caused by termination of eyeball development after closure of the embryonic fissure. The condition is occasionally sporadic, and can be either autosomal dominant or recessive. The main clinical manifestations are microcornea, 1 shortened axial length, 2 narrow palpebral fissure 3 and thickened scleral wall,4,5 with complications including glaucoma, uveal effusion, exudative detachment of the retina and intraocular haemorrhage being common.
The majority of research into pure microphthalmia has concentrated on the retina, with the result that pathological changes to the cornea are not well understood. The aims of the present study were to determine the typical corneal changes of pure microphthalmia using a corneal topography system, and identify characteristics that may assist in early diagnosis.
Patients and methods
Study population
This prospective case–control study recruited patients with pure microphthalmia who attended the Department of Ophthalmology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China or Department of Ophthalmology, Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China, between October 2011 and June 2014. Exclusion criteria were: factors influencing refractive errors (including keratoconus, corneal laser surgery, trauma, etc); history of contact lens use; familial keratoconus; chronic keratitis and conjunctivitis; atopic disease; other systemic disease. Patients with secondary glaucoma were required to maintain normal intraocular pressure, a transparent cornea (determined via corneal endothelial mirror), a normal ratio of hexagonal cells to corneal endothelial cells and normal cell densities.
The control group comprised healthy age and sex-matched volunteers recruited from individuals undergoing routine health screening at the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China with uncorrected visual acuity score > 1.0, no history of trauma, no contact lens use, no refractive surgery, and normal eye development.
The study was approved by the ethics committees of the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province and the Third Hospital of Nanchang City, Nanchang, Jiangxi Province, China, and was performed in accordance with the Declaration of Helsinki for research involving human subjects. All participants provided written informed consent prior to enrolment.
Diagnosis
All participants gave a detailed disease history and underwent slit-lamp examination, inspection shadow optometry, automatic refraction meter examination and corneal topography. Ocular axial length was measured with A-mode ultrasonic diagnostic equipment, with the mean of five repeated measurements used for analysis.
Corneal topography
All participants underwent corneal topography analysis using the Orbscan IIZ® Corneal Topography System (Bausch and Lomb, Bridgewater, NJ, USA). With the participant seated, the lower jaw was lifted and the head restrained with the eyes looking at the front lamp. The eyes were kept open with light focusing at the centre of the pupil for 2 s, and corneal images were exported to a computer system. Images included a colour-code chart, anterior and posterior corneal surface elevation maps, a corneal surface gravity map and refractive corneal thickness figures. A total of nine corneal regions were identified, analysed and read.
Study parameters included central thinnest corneal depth, degree of corneal astigmatism (mean A), simulation of corneal astigmatism (sim A), mean keratometry (mean K), simulated keratometry (sim K), irregularities in the 3 - and 5-mm zones, and the mean thickness of nine distinct corneal regions (2 mm diameter circles, 3 mm from the optical axis; one at the central cornea and eight in the periphery). Corneal topography was classified based on anterior corneal surface refraction (round, oval, symmetrical bowknot, asymmetric bowknot and irregular), corneal surface elevation maps (symmetrical crest, asymmetric ridge, incomplete crest, island, and unclassified) and corneal thickness maps (circular, oval, eccentric circular and eccentric oval).
Each eye was examined three times and the best corneal topography images were analysed. When the image of the central cornea was unclear due to dry eye, eye movement, poor eye fixation or blinking, the examination was repeated until a distinct image was obtained. Binocular images were used for statistical analyses.
Statistical analyses
The sample size for the study was set to 12 based on the equation n = 15.6R + 1.6 with 80% confidence. Data were presented as mean ± SD (range). Between-group differences in sex were analysed using contingency tables. Data regarding age, axial length, dioptre, corneal refractive power and corneal topography parameters were compared using one-way analysis of variance or Student’s t-test. Function and sensitivity indices were determined using discriminant analysis. All statistical analyses were performed using SPSS® version 19.0 (SPSS Inc., Chicago, IL, USA) for Windows®. P-values < 0.05 were considered statistically significant.
Results
The study recruited 12 patients with pure microphthalmia (4 male/8 female; mean age 22.0 ± 2.3 years; age range 6–44 years) and 12 control subjects (5 male/7 female; mean age 21.6 ± 2.8; age range 6–44 years). There were no statistically significant between-group differences in age or sex.
Optical characteristics in patients with pure microphthalmia (PM) and healthy control subjects (n = 12 subjects [24 eyes] per group).
Data presented as mean ± SD.
P < 0.05 vs control; one-way analysis of variance or Student’s t-test.
D, dioptre.
Corneal topography parameters (Orbscan IIZ® Corneal Topography System; Bausch and Lomb, Bridgewater, NJ, USA) in patients with pure microphthalmia and healthy control subjects (n = 12 subjects [24 eyes] per group).
Data presented as mean ± SD (range) or n eyes (%).
Data from 3-mm zone.
> 46.50 D.
P < 0.05 vs control; one-way analysis of variance or Student’s t-test.
D, dioptre.
Corneal thickness (µm) in patients with pure microphthalmia and healthy control subjects (n = 12 subjects [24 eyes] per group).
Data presented as mean ± SD.
P < 0.05 vs control; one-way analysis of variance or Student’s t-test.
Corneal topography images of an 8-year-old female patient (Figure 1 a and b) show visibly different curvature of the anterior corneal surface to that of an 8-year-old female control subject (Figure 1 c and d).
Corneal topography images generated using the Orbscan IIZ® Corneal Topography System (Bausch and Lomb, Bridgewater, NJ, USA) in (a, b) an 8-year-old female with pure microphthalmia and (c, d) an 8-year-old female healthy control subject. (a) Map of anterior corneal surface revealing a steep central region with increasing steepness in peripheral areas. The shape of the cornea was eccentric circular. (b) Corneal thickness graph showing near normal central thickness (518µm) and significantly thickened peripheral cornea, with small eccentric oval morphology. (c) Map of anterior corneal surface showing gradual increase in the radius of the cornea from the centre to the periphery, with oval morphology. (d) Corneal thickness graph showing the thinnest area is located in the central area of the cornea (503 µm), with eccentric large oval morphology. The colour version of this figure is available at: http://imr.sagepub.com.
Discussion
Pure microphthalmia is a rare congenital eye disease characterised by small eye volume (60% of normal sagittal diameter, vertical diameter 14–17 mm, axial length < 20 mm, corneal diameter < 10 mm). The prognosis is poor, and patients are prone to secondary glaucoma, uveal effusion and other fundus diseases. Pathological examination of the eye reveals abnormalities in the arrangement of scleral collagen fibres together with glycosaminoglycan deposition, 6 leading to the formation of a thickened and impermeable sclera. 7 This results in obstructed vortex venous backflow and subsequent chronic choroidal effusion, ciliary body,choroidal detachment and nonporous retinal detachment. 8 The size of the anterior segment of the eye in is normal patients with pure microphthalmia, but the volume ratio of the crystalline lens is significantly increased. 3 In addition, choroidal detachment can push the lens iris diaphragm forwards so that it bulges and impinges on the anterior chamber, leading to secondary angle closure glaucoma. 9 Shortening of the posterior segment can lead to subtle retinal folds, choroidal folds, uveal effusion syndrome and pigmentary retinopathy. 10 Diagnosis of pure microphthalmia depends largely on clinical presentation and associated ocular imaging, including type A or B ultrasonography and ultrasound biomicroscopy.
Patients with pure microphthalmia exhibited a shortened eye axis, smaller corneal diameter and high central corneal curvature, as well as significantly higher mean K, sim K, mean A and sim A compared with control subjects in the present study. In addition, 75% of eyes from patients pure microphthalmia exhibited false keratoconus. Changes in corneal shape and thickness may prove useful for a greater understanding of pure microphthalmia.
The shape of the central cornea is important for understanding its refractive index. Thickness measurements at nine corneal locations determined that 75% of eyes in our patient group were in a state of false keratoconus. In patients, the central and temporal corneal areas were the thinnest, while the thickest areas were in the nasal and superior regions. This may be due to glycosaminoglycan depositions in the scleral and corneal fibres resulting in abnormal collagen or elastic fibres, or damage and thickening of the sclera and cornea. Since central corneal thickness may affect intraocular pressure, 11 its measurement could help with correct diagnosis of early glaucoma in patients with progressive pure microphthalmia.
The present study has several limitations, including its small sample size and bias associated with the single-centre design.
In conclusion, we describe changes in corneal morphology that could be useful in borderline situations to confirm the diagnosis of pure microphthalmia.
Footnotes
Declaration of conflicting interest
The authors declare that there are no conflicts of interest.
Funding
This research was funded by the National Natural Science Foundation of China (No: 81160118, 81400372, 81460092), Clinical Medicine Research Special-purpose Foundation of China (No: L2012052), Jiangxi Province Voyage Project (No: 2014022), Jiangxi province Degree and Postgraduate Education Reform Project (No:2015), Science and Technology Platform Construction Project of Jiangxi Province (No:2013116), Youth Science Foundation of Jiangxi Province (No: 20151BAB215016), Technology and Science Foundation of Jiangxi Province (No: 20151BBG70223), Jiangxi Province Education Department Youth Scientific Research Foundation (No: GJJ14170), and the Health Development Planning Commission Science Foundation of Jiangxi Province (No: 20155154), Scholar Project of Ganjiang River(2015).