Depositions and degenerative diseases of the cornea, sclera, and conjunctiva encompass a wide spectrum of pathologies. Degenerative diseases are common and usually result from physiologic changes related to aging, long-standing environmental insults, or systemic disease. Depositions typically are related to drug exposure or systemic illness. In this article, we review the clinical characteristics, pathophysiology, and treatment options of various depositions and degenerations of the conjunctiva, cornea, and sclera. Clinicians need to be able to recognize these conditions, as an appropriate ophthalmologic diagnosis may uncover an undiagnosed systemic disorder.
Key points
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Depositions and degenerative diseases of the cornea, sclera, and conjunctiva encompass a wide variety of pathologies. Many intricate processes and factors contribute to the development and progression of these conditions.
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Degenerations often are related to aging and can range in their clinical and visual significance. Depositions often reflect the use of certain systemic pharmacologic therapies or underlying systemic disease.
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Treatment of these conditions can range from conservative topical measures to surgical management. Interdisciplinary collaboration may be instrumental, given many of these conditions are indicative of an underlying systemic issue.
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Multifaceted and multidisciplinary challenges are posed by the diagnosis and management of anterior segment depositions and degenerations. However, promising developments in understanding both the pathophysiology and treatment are on the horizon.
Introduction
Depositions and degenerative diseases of the cornea, sclera, and conjunctiva encompass a wide spectrum of pathologies.
Degenerative diseases are common, usually resulting from physiologic changes related to aging, long-standing environmental insults, or systemic disease. Degenerations are a distinct entity from dystrophies, and it is rare for degenerations to stem from a genetic condition. Depositions are typically related to drug exposure or systemic illness. The deposited material may reach the eye through tears, aqueous humor, or even the perilimbal vasculature.
In this article, we review the clinical characteristics, pathophysiology, and treatment options of various depositions and degenerations of the conjunctiva, cornea, and sclera. Clinicians need to be able to recognize these conditions, as an appropriate ophthalmologic diagnosis may uncover an undiagnosed systemic disorder.
Significance
Conjunctiva
Pinguecula
Pingueculae typically appear as yellow-white elevated lesions on the bulbar interpalpebral conjunctiva, adjacent to the limbus with a predilection for the nasal conjunctiva ( Fig. 1 ). Risk factors include exposure to ultraviolet (UV) light, environmental exposures like wind and dust, and age [ ]. Histologically, pingueculae are characterized by elastoid degeneration of the subepithelial collagen [ ].
Pingueculae are benign growths and typically do not cause issues, although they may slowly enlarge over time. Some patients may develop recurrent inflammation, termed pingueculitis, which may be treated with topical lubrication or judicious short-term topical steroids.
Pterygium
Pterygia are wing-shaped fibrovascular proliferations of the conjunctiva onto the cornea ( Fig. 2 ). Similar to pingueculae, UV light along with environmental exposure contribute to its pathogenesis [ ]. Hence, the prevalence of pterygia is higher in individuals who live near the equator [ ].
The histopathology of pterygia also is similar to that of pinguecula in that they both are characterized by elastoid basophilic degeneration of subepithelial tissue. However, pterygia invade the superficial cornea. It may be clinically difficult to differentiate a pterygium from ocular surface squamous neoplasia (OSSN), although atypical elevation, feeder vessels, and rapid growth should raise suspicion for malignancy. Anterior segment OCT also can be used to evaluate for an abrupt change and thickening of the epithelium, which is characteristic of OSSN [ ].
Medical treatment with topical lubrication and short-term topical steroids can help alleviate irritation that may result from inflamed pterygia. Indications for surgical excision include persistent irritation, obscuration of vision due to growth into the visual axis, induced astigmatism, or restriction of motility. Excision with conjunctival autograft is considered the gold standard approach to excision due to the low recurrence rate [ ]. Excision with amniotic membrane graft can be considered, although it has higher recurrence rates [ ]. Adjunctive therapies offer varying degrees of benefit in conjunction with autografting. The most promising among adjunctive treatments is topical cyclosporine in reducing pterygia recurrence [ ]. Other adjuvant agents including mitomycin-C, 5-fluorouracil, and beta-irradiation also may be employed, although they bear the risk of adverse effects including corneal or scleral melt ( Fig. 3 , Table 1 ).
| Therapy | Mechanism of action | Advantages | Disadvantages | Complications |
|---|---|---|---|---|
| Beta-irradiation | Focal radiation with high-velocity electrons inhibits mitosis | Reduction in recurrence rate | No standard fraction/protocol, risk of toxicity | Scleromalacia, necrosis, scleral perforation, endophthalmitis, and cataract |
| Mitomycin-C | Alkylating agent inhibits RNA, DNA, and protein synthesis | Reduction in recurrence rate | Risk of toxicity, should be avoided if thin sclera | Scleral thinning, ulceration, and delayed conjunctival epithelialization |
| 5-Fluorouracil | Inhibits S phase of cell cycle | Reduction in recurrence rate | Controversial efficacy, risk of toxicity | Scleral thinning, corneal toxicity |
| Anti-vascular endothelial growth factor (VEGF) | Antiangiogenic agent administered as subconjunctival injections or topical drops | Reduction in recurrence rate with good tolerability | High cost and transient effect | Corneal epithelial defects and erosions |
| Topical cyclosporine A | Inhibits fibroblast proliferation | Good tolerability | Limited evidence | Corneal dellen irregularities |
| Collagen matrix implants | Induces regenerative wound healing, prevents scar formation | No risk of toxicity | Limited evidence | Foreign body sensation, recurrent inflammation, and tearing |
Concretions
Typically noted in elderly patients, as well as those with long-standing inflammation, conjunctival concretions present as multiple, small chalky yellow-white densities located in the subepithelial space of the palpebral conjunctiva or fornices [ ] ( Fig. 4 ). Concretions often remain asymptomatic while small in size but can induce irritation, injection, and photophobia if they enlarge or rub against the cornea if located under the tarsal conjunctiva of the upper eyelid.
The etiology of conjunctival concretions can vary, but chronic inflammation is thought to play a role, such as in cases of chronic conjunctivitis (vernal, atopic, trachoma, etc.) or meibomian gland disease [ ]. Concretions of the conjunctiva have also been linked to the recrystallization of eye drops such as sulfadiazine.
Concretions are primarily composed of mucinous and protein-rich secretions and debris from degenerating epithelial cells, confined to small subconjunctival alcoves where they may become calcified. On histochemical analysis, concretions stain positively for periodic acid-Schiff and mucicarmine [ ].
Treatment rarely is necessary. In cases of erosion through the epithelium, concretions can be removed at the slit lamp with forceps, a 30-gauge needle, or with a small chalazion curette [ ].
Conjunctivochalasis
Thought to be secondary to aging, conjunctivochalasis refers to redundant folds of healthy conjunctival folds characterized by excess laxity, usually located inferiorly and bilaterally [ ]. While typically asymptomatic, conjunctivochalasis can trigger foreign body sensation, epiphora secondary to tear outflow obstruction, dryness, or subconjunctival hemorrhage [ ].
Its etiology remains unclear; however, age, ocular surface disease and dryness, eye rubbing, and UV exposure are thought to be potential risk factors. Histologically, conjunctivochalasis typically appears like healthy conjunctiva; however, some cases can demonstrate mild inflammatory or elastotic changes, along with microscopic lymphangiectasia [ , ]. Elevated expression of matrix metalloproteinases (MMP-1 and MMP-3) has been observed in the fibroblasts of conjunctivochalasis specimens [ ].
In cases of severe conjunctivochalasis, the inferior tear meniscus can be altered by redundant tissue, thus disrupting the tear film. Management of conjunctivochalasis depends upon the degree of symptoms. Topical lubrication, topical antihistamines, or short courses of topical corticosteroids may be indicated accordingly. Thermal cautery to tighten and contract lax tissue, conjunctival excision, scleral fixation of the conjunctiva, or forniceal reconstruction with amniotic membrane have been used in refractory cases, with varying success.
Superior limbic keratoconjunctivitis
Superior limbic keratoconjunctivitis (SLK) is characterized by the inflammation of the upper tarsal and bulbar conjunctiva. Common symptoms include foreign body sensation, photophobia, ocular burning, and pain [ ]. The etiology is not well understood; however, it has been proposed that SLK is due to constant excessive laxity causing friction between the superior bulbar and tarsal conjunctiva [ ]. An association exists between SLK and thyroid disease and keratoconjunctivitis sicca.
Clinical examination is characterized by the inflammation of the superior and bulbar palpebral conjunctiva, staining of the cornea adjacent at the superior corneal limbus, and sometimes corneal filaments ( Figs. 5 and 6 ).
Many different therapeutic modalities have been reported. Conservative therapies include topical lubrication and topical corticosteroids. For refractory cases, conjunctival resection, liquid nitrogen cryotherapy, and punctual occlusion may be considered [ ].
Amyloidosis
Characterized by extracellular hyaline deposits, amyloidosis can present in nearly any organ of the body, including various parts of the eye and its adnexa, ranging from the extraocular muscles to the trabecular meshwork. Involvement of the conjunctiva is rare. Typically, when it does present in the conjunctiva, it is as a primary, localized condition or mass, rather than a manifestation of systemic amyloidosis [ ]. Rarely, conjunctival amyloidosis may be triggered by blunt trauma [ ].
On clinical examination, conjunctival amyloidosis usually presents as a well-circumscribed, waxy, orange-yellow, or yellow-pink-colored vascularized or hemorrhagic mass [ ] ( Fig. 7 ). Such well-circumscribed lesions undergo excisional biopsy, while more diffuse lesions will undergo incisional biopsy. Histologic analysis is diagnostic, revealing eosinophilic material with classic Congo red staining and apple-green birefringence. Patients with localized conjunctival amyloidosis should be evaluated for primary systemic amyloidosis or lymphoma [ ].
Cornea
Coats white ring
Corneal foreign bodies may be found in any layer of the cornea, and those embedded past Bowman’s layer are most likely to scar. When an iron-containing foreign body is removed from the cornea, it may leave behind a small white ring in the corneal stroma known as a Coats white ring [ ]. Typically small (<1 mm diameter) with a gray-white color, Coats white rings contain fibrotic residue and iron. They only are visually significant if located centrally in the visual axis. Otherwise, they remain static and do not respond to topical therapies including steroids and require no intervention.
Spheroidal degeneration
Characterized by fine amber-yellow spherules that appear translucent, spheroidal degeneration can affect the cornea and/or conjunctiva ( Fig. 8 ). These proteinaceous droplet-like lesions can be found in the corneal stroma, Bowman’s membrane, the subepithelial layer, and within the epithelium itself in advanced cases [ ]. More commonly found in regions with extreme temperatures, sandy environments with high winds and low humidity, and high levels of direct/reflected sunlight [ ], spheroidal degeneration is also known as climatic droplet keratopathy. It also may be referred to as actinic keratopathy, Bietti’s band-shaped nodular dystrophy, or Labrador keratopathy (in reference to icy Labrador, Canada, where this condition has increased prevalence).
