Spheroidal degeneration is a degenerative disease in which yellowish-brown spherical deposits accumulate beneath the epithelium of the cornea and conjunctiva. Yellowish-white deposits accumulate beneath the epithelium along the palpebral fissure. It has many other names based on geographic location or predisposed races, such as climatic droplet keratopathy, chronic actinic keratopathy, Bietti’s nodular corneal degeneration, and Labrador keratopathy.
It is considered one of the degenerative diseases associated with ultraviolet exposure. It is common in tropical regions but rare in Japan. In southwestern Rajasthan, India, the prevalence of spheroidal degeneration is high due to high temperatures, sandstorms, and low rainfall 2). It is more common in men.
Fraunfelder et al. classify this condition into the following three types:
| Type | Characteristics |
|---|---|
| Primary corneal type | Occurs independently of ocular disease. Associated with aging. Bilateral. |
| Secondary corneal type | Secondary to long-standing ocular disease. Unilateral or bilateral. |
| Conjunctival type | Alone or secondary to corneal type. More common in elderly. |
Primary corneal type occurs unrelated to ocular disease and is associated with aging. Secondary corneal type is secondary to various ocular diseases such as glaucoma, corneal herpes, Fuchs endothelial dystrophy, and lattice corneal dystrophy. Conjunctival type is associated with pinguecula and pterygium.
According to the Fraunfelder classification, it is divided into three types. Primary corneal type (type 1) occurs bilaterally unrelated to ocular disease and is associated with aging. Secondary corneal type (type 2) is secondary to long-standing ocular diseases such as corneal herpes and glaucoma. Conjunctival type (type 3) is associated with pinguecula and pterygium and is more common in the elderly.
| Grade | Findings |
|---|---|
| Trace | Few lesions in the interpalpebral fissure of one eye |
| Grade 1 | Horizontal involvement across the interpalpebral fissure but not reaching the center |
| Grade 2 | Involves the central cornea but does not affect vision |
| Grade 3 | Involves the central cornea and reduces vision |
| Grade 4 | Lesion elevated in addition to Grade 3 |
Ultraviolet (UV) exposure is considered the most important environmental factor. It is associated with elastoid degeneration seen in pterygium and pinguecula. It is presumed that UV interaction causes serum proteins from the limbal vessels to diffuse into the cornea, leading to degeneration and accumulation.
Environmental Factors
UV exposure: The greatest risk factor. UV reflected from ice, snow, and desert areas contributes.
Climatic conditions: High temperature, low humidity, sandstorms, and low rainfall increase risk. Prevalence is high in southwestern Rajasthan, India2).
Occupational exposure: Burns from welding are also recognized as an occupational risk.
Individual Factors and Ocular Diseases
Aging: Incidence increases with age.
Pre-existing ocular diseases: Keratitis, lattice corneal dystrophy, glaucoma, etc., are risk factors for secondary corneal type.
Others: Dry eye, malnutrition, corneal trauma, and microtrauma from wind, sand, and ice are involved.
Because UV exposure is the greatest risk factor, the prevalence is high in high-latitude areas where UV reflects from snow and ice (e.g., Labrador region) and in low-latitude areas near the equator where UV is strong in desert regions. In southwestern Rajasthan, India, the prevalence of spheroidal degeneration is particularly high due to high temperatures, sandstorms, and low rainfall 2).
Clinical Diagnosis
Slit-lamp microscopy: Yellow-brown spherical deposits are observed under the corneal epithelium in the interpalpebral fissure. They appear droplet-like at low magnification but disappear at high magnification.
Johnson-Ghosh grading: The extent of the lesion and its impact on vision are evaluated from Trace to Grade 4.
Imaging Tests
Anterior segment OCT: Objectively evaluates the depth and extent of deposits. It can measure the depth of subepithelial fibrosis and anterior stromal scarring 1).
Histological examination: Stains eosinophilic with H&E and blue-green with toluidine blue. Not essential for diagnosis.
Usually asymptomatic and no treatment is required. Age-related changes progress slowly and often do not cause visual impairment.
In cataracts complicated by spheroidal degeneration, intraoperative visibility is reduced due to corneal opacity2). In areas where penetrating keratoplasty is difficult to perform, SICS (small incision cataract surgery) + IOL implantation is an effective option, with visual improvement achieved in 92.85% of patients2).
In a study of 56 cases of spheroidal degeneration with cataract in a tribal population in Rajasthan, SICS improved mean best corrected visual acuity (BCVA) from 2.3±0.67 logMAR preoperatively to 0.4±0.22 logMAR at one month postoperatively (P < 0.0001). 63.3% achieved vision of 6/6 to 6/122).
Superficial keratectomy and deep anterior lamellar keratoplasty (DALK) are effective for spheroidal degeneration. In Grade 3 cases, DALK has been reported to achieve visual acuity of 6/9 postoperatively 1). However, the cornea in spheroidal degeneration is hard, making big bubble formation difficult 1). Additionally, recurrence is possible after superficial keratectomy or superficial keratoplasty.
Pathologically, hyaline-like material accumulates in the subepithelium and Bowman’s layer. The deposited material is composed of proteins. It is thought to be granular protein secreted by keratocytes that deposits on adjacent collagen fibers.
Several hypotheses exist regarding the origin of the deposited material. A leading hypothesis proposes that plasma proteins (immunoglobulins and albumin) diffuse into the cornea from the limbal circulation and are denatured and accumulate due to ultraviolet radiation. Another hypothesis suggests that secretory products from the stroma or epithelium (incomplete collagen or degraded stromal collagen) deposit.
It is associated with elastoid degeneration seen in pterygium and pinguecula. Chronic tissue damage from ultraviolet radiation is considered a common pathological basis.
Under light microscopy, extracellular deposits of various sizes, spherical or elongated, are observed in the subepithelium, Bowman’s layer, and superficial stroma. In advanced stages, Bowman’s layer is focally disrupted or absent. Inflammatory cells are usually absent. Electron microscopy shows fine granular structures accumulating on collagen bundles.
The deposited material is composed of proteins. It is thought to be granular protein secreted by keratocytes that deposits on collagen fibers. A leading hypothesis is that plasma proteins (immunoglobulins and albumin) diffuse from limbal vessels and are denatured and accumulate due to ultraviolet radiation. It stains eosinophilic with H&E and blue-green with toluidine blue.
The efficacy of deep anterior lamellar keratoplasty for spheroidal degeneration has been reported. In cases of Grade 3 spheroidal degeneration treated with DALK, big bubble formation was difficult, so the procedure was converted to manual dissection 1). Because the cornea in spheroidal degeneration is hard, after big bubble formation, the host Descemet’s membrane bulged into the anterior chamber, causing secondary angle-closure glaucoma due to reverse pupillary block 1).
In a case of deep anterior lamellar keratoplasty for Grade 3 central spheroidal degeneration in a 65-year-old male, acute angle-closure glaucoma with intraocular pressure of 46 mmHg occurred on postoperative day 1. Anterior segment OCT revealed bulging of the host Descemet’s membrane and residual stroma. Angle closure was relieved by decompression of the big bubble, and visual acuity of 6/9 was achieved at 1 month postoperatively1).
In regions with high prevalence of spheroidal degeneration, the safety and efficacy of SICS for complicated cataracts have been investigated2). Among 124 patients with hard cataracts and ocular complications, 45.16% had concurrent spheroidal degeneration2). Although reduced intraoperative visibility due to corneal opacity leads to difficulty in capsulorhexis, no serious complications were observed2).
