Hyperopic Keratoconus, or Is This Something Else?

INTRODUCTION

Keratoconus is a syndrome with multiple etiologies. Idiopathic keratoconus is a bilateral, non-inflammatory, progressive thinning of the cornea that results in steepening and protrusion of the cornea, a condition known as ocular ectasia. It is characterized by progressive posterior corneal elevation, which draws the posterior surface of the cornea closer to the anterior surface. All cases of keratoconus are bilateral, but it can manifest asymmetrically. Keratoconic ectasia focal is located, which produces an irregular astigmatism pattern. As the condition progresses, changes in curvature can result in unevenly located astigmatism and myopic shifting.

Keratoconus often starts during adolescence and progresses until the 3rd or 4th decade. It affects both genders and all ethnicities.¹ Keratoconus has both genetic and environmental risk factors, such as eczema and constant rubbing of the eyes.² Corneal tomography should be used to find posterior corneal elevation and corneal ectasia, which confirmed the diagnosis of keratoconus.¹

Nanophthalmos, or complete microphthalmos, is defined by an axial length two standard deviations smaller than the average orbital length. It is due to the developmental arrest of both the anterior and posterior segments of the eye without other structural defects.³ Other manifestations of nanophthalmos include increased scleral thickness, a small cornea diameter, a shallow anterior chamber, and an increased lens-to-eye volume ratio.

A normal adult axial length is between 22 and 25 mm. There is no clear consensus as to the axial length that establishes the diagnosis of nanophthalmos. An axial length of less than 20.5 mm, two standard deviations below the mean, is currently used as a diagnostic benchmark.³

The posterior sclera is usually about 2 mm instead of 1 mm thick, since nanophthalmos may restrict eyeball growth.⁴ There may be an abnormally large amount of proteoglycan between scleral fibers, causing an irregular variation in the thickness of the sclera.⁵

The corneal diameter in patients with nanophthalmos is usually less than 11.00 mm, and the corneal curvature is usually more than 46.00D.⁶ Patients have an increased risk of secondary angle closure glaucoma due to an anterior chamber depth less than 2.66 mm, whereas a normal depth ranges between 3.14 and 3.60 mm.⁷

In nanophthalmic patients, the lens thickness either remains normal or appears enlarged. While a normal lens-to-eyeball volume ratio is about 4%, in nanophthalmic eyes, this ratio increases to between 11 and 32%, resulting in high hyperopia ranging from +7.00D to +20.00D.⁸ Possible fundus abnormalities include increased choroidal thickness, increased retinal thickness, papillomacular folds due to cell crowding in the neuroretinal layer, a crowded optic disc, and an absent or hypoplastic foveal avascular zone.^9,10

The etiology of nanophthalmos is varied. Many cases appear to be associated with a genetic mutation, although it may occur sporadically. Nanophthalmos can occur in isolation or as a part of a syndrome. To date, 5 genes have been associated with the inherited form of nanophthalmos: MFRP, TMEM98, PRSS56, BEST1, and CRB111.

In this paper, we are reporting about a patient who initially presented with high hyperopic keratoconus, and subsequently was shown to have nanophthalmos. We propose that Leber’s congenital amaurosis primarily caused the patient’s poor visual acuity.¹¹

CASE PRESENTATION

A 44-year-old Mennonite man was referred to our specialty contact lens clinic for blurry vision due to keratoconus. The patient reported wearing glasses as a child and rubbing his eyes frequently. He noted progressively deteriorating vision in his left eye. He denied past ocular trauma or infection, other relevant illnesses, and a family history of blindness, poor vision, or keratoconus. However, his medical records were limited due to his religious background.

His manifest refraction was +16.25–0.50 × 020 and +14.25–7.25 × 100, with BCVAs of 20/150 and 20/400 in his right and left eyes, respectively. The anterior segment of his exam showed significant floppy eyelids in both eyes and apical thinning with apical haze in his left eye.

Computerized corneal tomography was performed prior to contact lens fitting. The refractive map of his right eye showed a relatively normal curvature, with a steep K of 48.1D and a flat K of 47.6D. It revealed a corneal thickness of 591 um centrally. The curvature map of his left eye exhibited significant steepening inferiorly, covering two thirds of his cornea along with a steep K of 67.3D, a flat K of 65.2D, and a central corneal thickness of 434 um (Fig. 1A). The Berlin-Ambrosio Enhanced Ectasia Display also demonstrated an extreme posterior elevation of +114 um in the left eye. Other abnormalities found in the left eye were a Kmax of 77.3D and a total deviation (D) of 24.70D (Fig. 1B).

The total D value is used to predict corneal ectasia and assists in the detection of keratoconus by incorporating anterior and posterior elevation, corneal thickness, and best fit sphere. A total D value of 1.88 or more is suggestive of keratoconus.¹²

While the diagnosis of keratoconus was suggested due to the presence of a highly irregular astigmatism, corneal ectasia with posterior elevation, and the absence of ocular inflammation in his left eye, the absence of bilateral findings caused us to question an idiopathic etiology. Steepening of the cornea generally causes a myopic shift, rather than a hyperopic shift as seen in our patient.

Computerized corneal tomography findings were used to help to fit the patient into specialty scleral lenses, and suggested that he might need a higher-order aberration (HOA) correction. Higher-order aberration are significant irregularities caused by corneal scars, ocular trauma, diseases, or surgeries. These aberrations often cannot be corrected with traditional glasses or standard contact lenses but can be addressed with HOA corrective scleral lenses.

With the scleral lenses in place, an over-refraction of +21.00 sph and +21.25–1.25 × 090 in the right and left eyes, respectively, resulted in a BCVA of 20/50 OD and 20/70 OS. Previously, the BCVA was 20/150 OD and 20/400 OS with glasses. Despite the improvement, the patient still experienced significant glare and distortion in his vision. We used the x-wavefront aberrometer and found that the right eye had an HOA value of 4.42 due to a high third order horizontal coma. The left eye had an HOA value of 2.23 with aberrations, including a third order horizontal coma and a fourth-order vertical secondary astigmatism. An HOA value greater than 0.40 is significant.

Given that keratoconus is typically associated with high myopia, further examinations in this atypical case were conducted. A dilated fundus exam was performed along with an Axial length scan (A-scan) and an optical coherence tomography (OCT) macula. The patient’s fundus revealed hypoplastic nerves, dominant drusen, and faint traces of mid-peripheral bony spicules in both eyes (Fig. 2). The A-scan measured axial lengths of 16.14 mm and 16.21 mm in the right and left eyes, respectively. The A-scan also revealed an anterior chamber depth of 3.02 mm in the right eye and 3.36 mm in the left eye, while the OCT macula showed a thickened macula of 442 um OD and 453 um OS. The line scan across the macula also revealed the absence of the fovea-pit in both eyes; however, both the photoreceptor integrity line (PIL) and retinal pigment epithelium (RPE) lines remained intact (Fig. 3). These abnormal parameters correlate with the expected findings in patients with nanophthalmos. Since nanophthalmos is highly associated with high hyperopia, this diagnosis would explain why our patient does not exhibit the typical myopic shift seen in other keratoconus cases. Bilateral optic nerve hypoplasia and the lack of fovea in both eyes would also explain his poor visual acuity and reduced color vision.

An electroretinogram (ERG) and fundus autofluorescence (FAF) were performed to further investigate the patient’s condition. The ERG showed abnormal receptor activities under both photopic and scotopic conditions. Under photopic conditions, while the a-wave corresponding to photoreceptors was normal, the b-wave, representing bipolar, horizontal, and amacrine cells, showed reduced activity. Bipolar cells were also tested under ‘light-adapted 3.0 flicker,’ which appeared abnormal for both eyes. Under dark adaptation, a diminished response could be seen in both a- and b-waves, suggesting poor visual potential in dim light, especially with larger stimuli. The multifocal electro retinal gram (mfERG) showed diminished photoreceptor activity in both eyes (Fig. 4).¹³ The FAF revealed scattered hyper-autofluorescence, indicating increased RPE lipofuscin, which corresponded with RPE dysfunction (Fig. 5).¹⁴ Taking all our findings into account, we strongly suspect that Leber’s congenital amaurosis is our patient’s underlying disorder. The patient denied genetic testing, so we were unable to reach any definitive conclusions.¹⁵

LEBER’S

Leber’s congenital amaurosis (LCA) refers to a group of diseases that cause severe vision loss in infancy. The vision loss is due to abnormal function and later degeneration of the retina A 2013 Study by Mark Elder. “Leber’s Congenital Amaurosis and its Association with Keratoconus and Keratoglobus” in the Journal of Pediatric Ophthalmology and Strabismus, show 10 keratoconus case in 35 children with LCA, resulting in a 29% correlation factor.^11,16 1 of 35 having Keratoglobus at 3% correlation factor.¹⁷ A 2009 study by Tim McMahon and colleagues, in Investigative Ophthalmic Visual Science. They found 16 primary Adult ages 13–74 patient with LCA, 5 had Keratoconus with a 31% association rate, and 1 of the 16 had Keratoglobus with a 6% association rate.¹⁸ When genetic testing was analysis, 2 key gene mutations were found as cooperating. The CRX and CRB1 genes were both found to be mutations in Leber’s and Keratoconsus (Tables 1 and 2).¹⁹

DISCUSSION

We suspect the etiology of our patient’s visual dysfunction is a genetic mutation. There are currently only five known genes associated with the inherited form of nanophthalmos: MFRP, TMEM98, PRSS56, BEST1, and CRB111. CRB1 is the only gene among the five that has been linked to keratoconus through LCA. CRB1 codes for a transmembrane protein in the inner segment of photoreceptors. It is important for the neuronal development of the retina, and mutations in this gene have been linked to various retinal dystrophies, including LCA.¹¹ Ocular manifestations of LCA includes keratoconus, photophobia, nyctalopia, vision loss, high hyperopia, nystagmus, abnormal pupillary response, chorioretinal atrophy around the fovea, boney spicules, and optic nerve abnormalities. The ERG of patients with LCA will also show abnormal responses in both photopic and scotopic conditions, in addition to an abnormal mfERG17. Therefore, we hypothesize that our patient has a CRB1 genetic mutation causing both nanophthalmos and LCA.

CONCLUSION

This case presented a rare instance of high hyperopia in a patient with keratoconus, prompting us to perform a thorough investigation, which led us to suspect a mutation in the CRB1 gene causing nanophthalmos and LCA.

REFERENCES

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