Cornea plana in a family from Pakistan: Case series and literature review on the principles of management

Abstract

Cornea plana (CP) is a rare ocular condition existing in two distinct clinical and hereditary forms: a milder, autosomal dominant type I and a more severe, autosomal recessive type II. The condition is more commonly found in Finnish, Saudi, and Czech families. We report three brothers from a consanguineous marriage that presented with complaints of decreased vision of varying degrees. All three of them have blue, thick, and hazy corneas with shallow anterior chamber depths. The additional features of CP type II were seen in the older two brothers including arcus lipoids, ill-demarcated limbus, and an accommodative squint. They were managed by the correction of refractive errors through spectacles and detailed counseling with follow-up visits to look for progressive complications. The management is mainly centered around optically or surgically correcting the developmental anomalies. This is complimented with proper genetic counseling and regular follow-up visits to look for and manage complications. There are, however, novel therapies that can be considered in these patients including corneal transplants or corneal stromal stem cellular therapies.

Introduction

Cornea plana (CP) is a rare hereditary condition, characterized by flattening of the corneal curvature making it like that of the sclera and leading typically, to hypermetropia and a hazy corneal limbus. It presents as either mild, autosomal dominant type 1 (CNA1, MIM 121400) or more severe, autosomal recessive type II (CNA2, MIM 217300), both of which are attributed to chromosome 12q21,33 through linkage analysis.[1] The condition is characterized by a flat corneal curvature, marked hyperopia due to low refractive power, and consequent accommodative esotropia. Other features include various cornea anterior segment abnormalities without systemic problems.[2,3]

Corneal thickness is a multifactorial genetic trait in which corneal stroma accounts for about 90% of the total thickness. It is composed of special interwoven type 1 collagen fibrils arranged uniformly. These collagen fibrils are interlinked with multiple other matrix substances.[4] Keratocan is a small leucine-rich proteoglycan, whose core is composed of leucine-rich regions which allow stacking into arched β-sheets, that stabilize its three-dimensional structure and is required for fibrillogenesis.[2]

Although the condition has a global distribution, it is typically seen within the Finnish, Saudi, and Czech Populus.[1,2] Here, we present a set of three siblings diagnosed with CP. To our knowledge, these are the first cases of CP reported in Pakistan.

Case Reports

Three brothers were brought to our ophthalmology clinic by their mother with complaints of decreased vision of varying degrees. The family was from a lower socioeconomic class and had presented from Mianwali, Punjab, Pakistan. They are born of consanguineous marriage and as per their mother, had a first-degree cousin already diagnosed with CP. The family tree is shown in a pedigree in Figure 1.

Figure 1.

Pedigree of the family

Case 1

The elder brother an 11 years old had complaints of painless decreased acuity for both near and far vision since childhood along with an inward deviation of the left eye. His visual deterioration was gradually worsening and progressive and after multiple hospital visits, had been using corrective glasses which resolved both complaints since he was 3 years old. His past birth, developmental, surgical, and medical history was unremarkable.

Unaided visual acuity was 6/90, N14 in the right eye, best corrected to 6/26 with + 13.5/+1.00 × 180° and 6/90 and N14 in the left eye, best corrected to 6/30 with + 14.5/+1.25 × 174°. On examination, he had small corneas with an apparent bluish haze and peripheral opacities – particularly in the superior part. We also noticed coarse facial features including a broad nose and low-set ears. His left eye was deviated inward, as shown in Figure 2, and the corneal reflection was displaced 2 mm temporally. His extraocular movements were of full range bilaterally. He had symmetrical 360° pannus formation in both eyes giving a horizontal, almond-like appearance to the corneas visible in Figure 3. The corneas had curvatures similar to that of the sclerae. The corneoscleral limbus was poorly demarcated and had a 2 mm × 2 mm well-demarcated central discoid endothelial button-like plaque. On gonioscopy, open angles were demonstrated with normal angle structures. On tonometry, his intraocular pressures (IOP) were 15 mmHg bilaterally and the axial lengths were 24 mm bilaterally. On keratometry, the readings were OD: K1 – 29.8, K2 – 30.2 and OS: K1 – 29.9, K2 – 30.2. Fundoscopy showed healthy maculae and was otherwise unremarkable. An automated videokeratoscopy (VKS) confirmed the marked corneal flattening and other slit-lamp examination findings.

Figure 2.

Eyes of the three brothers: the bluish haze, poorly demarcated corneoscleral limbus, broad nasal bridge, and left-sided accommodative esophoria can be seen in the elder brother’s eyes; bluish haze, poorly demarcated corneoscleral limbus, and right-sided accommodative esophoria can be seen in the middle brother’s eyes; bluish haze and poorly demarcated corneoscleral limbus can be seen in the younger brother’s eyes

Figure 3.

Slit-lamp examination of the elder brother’s eye showing small cornea, pannus formation, poorly demarcated corneoscleral limbus, and a 2 mm × 2 mm plaque

Case 2

The middle brother a 5 years old recently developed painless and persistent decrease in vision. His mother recalled that he had been facing difficulty while reading despite using the thick and heavy glasses prescribed by a local doctor since he was 3 years old. His past birth, developmental, surgical, and medical history was unremarkable.

Unaided visual acuity was 6/60, N12 in the right eye, best corrected to 6/20 with + 15.5/+1.50 × 180° and 6/60 and N12 I the left eye, best corrected to 6/20p-2 with + 16.5/+1.00 × 90°. On examination, he had small corneas with an apparent bluish haze. The Hirshberg corneal reflex test was central with glasses bilaterally, but the corneal reflection was displaced 1 mm temporally in the right eye without glasses. His right eye was deviated inward, as shown in Figure 2. His extraocular movements were of full range bilaterally. On slit-lamp examination, he had symmetrical bilateral 360° conjunctivization of the cornea – predominantly in the superior and inferior part, giving a horizontally oval appearance. There was poor limbal demarcation, and the corneas were thicker centrally and appeared flat, having curvatures similar to that of the sclerae. The anterior chambers were moderately shallow but gonioscopy revealed open angles with normal angle structures. On tonometry, his IOPs were 11 mmHg in the right eye and 13 mmHg in the left eye. An automated VKS confirmed the marked corneal flattening and other slit-lamp examination findings. Anterior-segment optical coherence tomography of both eyes demonstrated 360° open angles with a flat cornea. His corneal diameters were less than normal in both eyes (OD: R1 – 11.4 mm, R2 – 10.15 mm and OS: R1 – 12.87 mm, R2 – 11.89 mm). Central corneal thickness was 591 μm in the right while 565 μm in the left eye and axial length was normal in both eyes (OD: 23.5 mm and OS: 23.75 mm). Fundoscopy showed healthy maculae and was otherwise unremarkable.

Case 3

The younger brother a 2 months old was brought with complaints of blue corneas similar to his two elder siblings described above, as shown in Figure 2. He was examined under anesthesia and had corneal diameters of OD: R1 – 9 mm, R2 – 9.5 mm and OS: R1 – 9.5 mm, R2 – 9.7 mm. IOP was bilaterally 14 mmHg, and retinoscopy revealed a refractive error of + 16.00 DS in both eyes. Anterior segment examination revealed that the cornea had curvatures similar to that of the sclarea and there was a central button-like plaque at the level of endothelium of both eyes. Fundoscopy showed healthy maculae and was otherwise unremarkable. VKG confirmed the findings of the flatter and thicker corneas.

Both parents did not have any clinical features like those of their children, as examined by the primary treating team. Based on the siblings’ clinical presentations, diagnoses of CP type II were made in all three siblings which were complicated by high hypermetropia and accommodative esotropia in the elder two. The patients’ parents were counseled regarding the benign nature of the disease, its congenital etiopathology, and regarding future pregnancies. Maximum refractive corrections were prescribed to the patients and a yearly follow-up was recommended to look for any complications of CP. Genetic testing for the disease could not carried out due to the family’s limited financial resources and a lack of accessibility to genetic studies in Pakistan.

Discussion

To our knowledge, this is the first case of CP reported in Pakistan. The underlying feature of CP is flattening of the cornea due to loss of its curvature leading to a shallow anterior chamber.[3] Conventionally, in autosomal dominant CP, the visual acuity is mildly affected and may even be normal and presents with an abnormally broad corneal limbus but with clear corneal parenchyma.[3] However, in autosomal recessive CP, the presentation is more severe. The features include centrally thick and hazy microcorneas, poorly demarcated limbus (with visible scleral encroachment), and marked hyperopia.[2,3] This can also be shown in Figure 4. Comparing the two, the corneal refractive power reduces from the normal 43D to a range of 33–40D in CP type I, but in type II, it is markedly reduced to 25–35D.[3]

Figure 4.

Clinical features in autosomal recessive CP. CP: Cornea plana

In addition, in CP type II, arcus lipoides, malformations of the iris (iris hypoplasia, anterior/posterior iris synechiae, etc.), slit-like displaced pupils, deep central corneal opacities, congenital ptosis, and a secondary convergent squint may be seen.[2,3] Furthermore, corneal ectasia, corneal hydrops, and idiopathic corneal decompensation are very rare findings that may also be present.[2] Further still, the condition may be complicated by ametropic amblyopia, restricted peripheral vision, posterior amorphous corneal dysgenesis, closed-angle glaucoma, varying cataracts, and/or deep horizontal band keratopathy.[2,3]

For CP type I, no underlying gene has been identified; however, for CP type II, mutations in the KERA gene that encodes for keratocan have been attributed to causing the condition.[1] The cornea constitutes the highest quantity of keratocan in the body (by dry weight) and most of it is distributed in the center, imparting strength, and structural stability.[2,4] The mutations causing the condition, maybe missense or nonsense but the loss of functional keratocan leads to the loss of the forward convex curvature of the cornea, prototypical for CP.[1] In our case, both parents were likely carriers of these mutations.

Keeping in view the rarity and complex nature of the disease, we developed in-depth guidelines on how to manage patients with CP. There are multiple components in managing this condition including patient education and proper counseling, correction of refractive error, cosmetic correction, maintaining follow–ups, and treating complications. Within which, the refractive error is the prime issue to correct that can be done through eyeglasses, contact lenses, or surgery.[5,6] It is worth mentioning over here that in most cases, complete correction is almost never achieved with routine spectacles or polymethylmethacrylate contact lenses, however, as Dada et al. argues that the best cosmetic and visual rehabilitation can be achieved by high-plus, low-water content, and lenticular soft lenses.[6]

Surgical options that may benefit patients include photorefractive keratectomy (corrects about 2D of hypermetropia), laser in situ keratomileusis (corrects about 4D of hypermetropia), laser thermal keratoplasty (corrects about 2D of hypermetropia), surface-based excimer laser (corrects about 4D of hypermetropia), and conductive keratoplasty. These options, however, may benefit if the refractive error is minor and nonprogressive but the loss of functional keratocan raises the question of whether these treatments will maintain the correction in the long run.[5]

An initial diagnosis of CP on ocular and slit-lamp examination should be followed by keratometry or VKS for the confirmation of the diagnosis. The first visit should also include a fundoscopic examination to look for both lenticular changes and macular degeneration as well as tonometry and gonioscopy to look for glaucoma. The same examinations may be repeated at annual follow-up visits. It is important to mention here that tonometry based on corneal thickness and curvature may be erroneous in patients with CP due to the underlying defect.[7]

For synechiae, cycloplegics, and anti-inflammatory medications may break adhesions; however, the literature on this is scarce.[7] Peripheral laser iridotomy with or without glaucoma medication maybe indicated if the patient is at risk or has developed glaucoma.[7] Rarely, CP can lead to or occur with lenticular changes in which cases have been reported of successful refractive correction through customized toric intraocular lens implantation. However, in such cases, high astigmatism, shallow anterior chamber depth, and short axial length are valid challenges to keep in mind during surgery.[8]

The patients must also be properly counseled regarding the etiopathogenesis and hereditary nature of the disease. This includes explaining to the patient that as with all Mendelian disorders, depending on whether the condition is autosomal recessive or autosomal dominant, there will be certain risks of transferring the mutation to their offspring making them either carriers or also affected.

It is also worth mentioning that there are multiple novel therapies that maybe initiated in these patients, but further research is required to study the short-term and long-term effects. This includes corneal transplantation and corneal stromal stem cellular therapy.[9,10] Corneal transplantation involves the transplant of a donor cornea which would have the normal curvature and biochemical structure. However, keeping in view, the corneal regeneration process initiating from the peripheral limbus to the center and the abnormal recipient curvature in CP, the long-term success of the transplant is questionable.[10] Cellular therapy with ocular and extraocular stem cells may correct the underlying deficiency of functional keratocan preventing the progression of the condition.[9]

Conclusions

Since the condition has no specific cure, the management is mainly centered around optically or surgically correcting the developmental anomalies. This is complimented with proper genetic counseling and regular follow-up visits to look for and to manage complications.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for the patients’ images and other clinical information to be reported in the journal. The guardian understands that the patients’ names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.