Peripheral Hypertrophic Subepithelial Corneal Degeneration

Etiology

The current etiology of PHSCD is largely unknown. Some reports suggest that PHSCD may occur after chronic ocular surface diseases such as dry eye disease, contact lens wear, or ocular surgery.[6] Others argue that PHSCD might be a primary disease.[4] A study reported that a case of PHSCD occurred soon after the patient underwent femtosecond-assisted laser-assisted in situ keratomileusis (LASIK), with resolution after superficial keratectomy.[6] Another study suggested that the human leukocyte antigen-B*44 allele and the 8.1 ancestral haplotype may be immunological factors that predispose patients to develop PHSCD, but the same authors reported a subsequent study's conclusions refuted this claim.[4][13]

PHSCD has been hypothesized to be associated with decreased tear film production and reduced tear film stability.[14] Study observations have shown decreased Schirmer test results (see Image. Schirmer Test Results) and tear break-up time scores in patients with PHSCD.[15] The Schirmer test quantifies the number of tears an eye produces, whereas the tear break-up time measures the time it takes for a dry spot to form on the cornea under fluorescein staining using the slit lamp.

The primary causes of PHSCD are:

• Chronic ocular surface inflammation, such as blepharitis, dry eye syndrome, and allergic conjunctivitis [16]
• Ocular trauma caused by mechanical force, chemical exposure, or surgical procedures [17]
• Age-related changes
• Genetic predisposition
• Environmental factors, such as ultraviolet radiation, pollutants, and allergens
• Systemic conditions (for example, autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus)
• Nutritional deficiencies, such as vitamins A and C
• Chronic infections [18]
• Previous ocular surgeries, such as pterygium excision and cataract surgery [19]
• Contact lens wear [20]
• Tear film abnormalities
• Exposure to toxic substances

Epidemiology

PHSCD typically occurs bilaterally and symmetrically, as observed in 81.6% of documented cases, and predominantly affects middle-aged women in White populations, with a woman-to-man ratio of 4:1.[1][13] The overall incidence rate of this condition is unknown due to the scarcity of reported cases. Regular ophthalmic evaluations and advanced imaging techniques help identify and manage PHSCD, providing better insights into its epidemiological patterns.[6]

Age groups: PHSCD is predominantly observed in older adults, typically those older than 50. Cases in younger individuals are rare but possible.[14]

Geographical distribution: Data on the specific prevalence of PHSCD in the United States are limited, but it is recognized among the older population during routine ophthalmic examinations. Similar to the distribution in the United States, PHSCD is observed in older adults globally, with no specific regions showing higher prevalence rates. The condition is likely underreported due to its often asymptomatic nature.[14]

General prevalence: The overall prevalence of PHSCD is considered low compared to other corneal degenerations. Due to its asymptomatic presentation in many cases, the condition might be more common than reported.[2]

Risk factors: Increased age, chronic ocular surface inflammation, history of ocular trauma, and previous ocular surgeries are significant risk factors.

Pathophysiology

The pathophysiological mechanisms of PHSCD are not yet understood but are believed to involve degeneration processes similar to those observed in Salzmann nodular degeneration.[5] Salzmann nodular degeneration and PHSCD are believed to occur due to the enzymatic destruction of the epithelial basement membrane through increased levels of matrix metalloproteinase-2, resulting in secondary deposition of extracellular matrix components and a fragmented or absent Bowman layer.[4][21][22] 

However, PHSCD tends to have larger and more circumferential corneal opacities compared to Salzmann nodular degeneration and typically has no presence of inflammation or preceding episodes of keratitis.[2] The fibrosis in PHSCD may extend to the mid-periphery but always spares the central cornea. The current literature has not described any systemic diseases or conditions definitively associated with PHSCD.

Histopathology

Histopathological findings of tissue samples from patients with PHSCD may include corneal epithelial thinning with a discontinuous, fragmented, or porous basement membrane and fibrosis between the epithelium and an absent or degenerated Bowman layer positive for vimentin staining. Acute or chronic inflammation may be absent in observed specimens.[4]

Key histopathological characteristics of PHSCD include:

• Subepithelial fibrosis: The primary histopathological feature of PHSCD is the presence of fibrous tissue beneath the corneal epithelium. This fibrous tissue is composed of collagen fibers and fibroblasts responsible for the proliferation and deposition of the fibrous material.[4]

• Disorganization of collagen fibers: The collagen fibers in the subepithelial region are disorganized, leading to the characteristic whitish opacity observed clinically.[23]

• Infiltration of inflammatory cells: Chronic inflammation is often associated with PHSCD. Histopathological slides may show infiltration of inflammatory cells, such as lymphocytes and macrophages, in the cornea's subepithelial and superficial stromal layers.

• Thickening of the basement membrane: The basement membrane, which separates the epithelium from the underlying stroma, may be thickened, contributing to the irregularities observed on the corneal surface.

• Absence of vascularization: Unlike other forms of corneal degeneration that may involve neovascularization, PHSCD typically does not show new blood vessel formation within the fibrotic areas.[24][25]

History and Physical

Obtaining a comprehensive medical history and performing a thorough physical examination are critical when evaluating patients with suspected PHSCD.

History

• Patient demographics: PHSCD typically affects older adults, with the most common cases occurring in those 50 or older.

• Symptoms: Patients with PHSCD typically present with bilateral decreased visual acuity due to astigmatism, a mild itching or burning sensation, a foreign body sensation, or a conjunctival injection. Some patients may also be asymptomatic.[1][3] Blurred vision can occur if the central cornea is involved.[26][27]

• Previous ocular conditions: A history of chronic ocular surface inflammation, such as blepharitis or dry eye syndrome, prior ocular trauma or surgeries, such as cataract surgery or pterygium excision, and exposure to environmental irritants may be present.[6]

• Systemic conditions: Patients may or may not have a history of systemic autoimmune diseases or nutritional deficiencies such as vitamin A or C deficiencies.[27]

Physical Examination Findings

• Slit-lamp examination findings may include:
• Bilateral, symmetric, whitish, or opaque subepithelial deposits, primarily in the peripheral cornea, forming a ring-like pattern in the periphery may be observed.
• The central cornea is typically clear, but extensive peripheral involvement can encroach upon the central area.
• Superficial neovascularization may also be observed at the base of the fibrosis.[4][10]
• Linear iron deposits may also be observed along the central edge of the opacification.[2]

• Inflammation: Signs of chronic inflammation may be present in the conjunctiva or eyelids.[28]
• Corneal surface: The affected areas may show irregularities in the corneal surface due to subepithelial fibrous tissue proliferation. 
• Visual acuity is typically preserved if the central cornea remains unaffected but can be reduced if fibrous tissue extends centrally.
• Light sensitivity: Some patients may report increased sensitivity to light (photophobia).[14]

Evaluation

PHSCD is a relatively rare corneal disorder that necessitates a comprehensive evaluation. Evaluating patients with PHSCD requires a multifaceted approach involving detailed clinical examinations, laboratory tests, specialized imaging techniques, and adherence to national and international guidelines. Following guidelines from organizations such as the American Academy of Ophthalmology (AAO), European Society of Cataract and Refractive Surgeons (ESCRS), International Council of Ophthalmology (ICO), and National Institutes of Health (NIH) ensures a comprehensive and standardized approach to diagnosing and treating patients with PHSCD.

Clinical Examination

• Manifest refraction: The first step in evaluating PHSCD is manifest refraction to quantify the patient's refractive error and cylindrical astigmatism. Manifest refraction may show a cylindrical astigmatism of 2.0 diopters or more.

• Slit-lamp examination: Slit-lamp biomicroscopy should be used to assess the clinical signs of PHSCD and rule out other diagnoses. Findings may include peripheral and circumferential subepithelial fibrosis in both eyes, associated neovascularization or pannus, and linear iron deposits along the central edge of the areas of opacification.[2]

• Visual acuity test: This test helps determine the extent of visual impairment caused by the corneal changes.

• Specular microscopy: This technique evaluates the health of the corneal endothelium, which can be affected by chronic corneal conditions such as PHSCD.

Laboratory Tests

• Tear film analysis: This evaluation includes tests such as tear break-up time, Schirmer test, and ocular surface staining to assess the quality and quantity of the tear film. Chronic ocular surface diseases can often coexist with tear film abnormalities.

• Corneal sensitivity test: Measuring corneal sensitivity can help determine the extent of corneal nerve involvement that can be affected in degenerative conditions.[5]

Radiographic and Other Imaging Techniques

• Corneal topography: This imaging technique maps corneal curvature, revealing any irregularities or elevations due to hypertrophic changes. Corneal topography may demonstrate flattening or thickening of the cornea at areas of fibrosis.[4] Assessing the corneal surface's shape is crucial for planning interventions.

• Anterior segment optical coherence tomography: Providing detailed images of the corneal structure is particularly useful in assessing the depth and extent of subepithelial deposits. Anterior segment optical coherence tomography (AS-OCT) may show continuous, homogenous, well-demarcated hyperreflective subepithelial bands associated with hyperreflectivity in the anterior stroma.[3]

• In vivo confocal microscopy: This imaging modality allows in vivo visualization of the corneal layers at a cellular level, helping distinguish PHSCD from other corneal dystrophies or degenerations.

• Ultrasound biomicroscopy: This imaging procedure is helpful in cases where AS-OCT is inconclusive. Ultrasound biomicroscopy provides high-resolution images of the anterior segment.[29]

Biopsy 

• A biopsy of the affected perilimbal areas may be considered to rule out conjunctival intraepithelial neoplasia.[15][30][31]

National and International Guidelines

• American Academy of Ophthalmology: The AAO provides guidelines for the diagnosis and management of corneal degenerations and dystrophies, including the use of slit-lamp biomicroscopy, corneal topography, and AS-OCT as standard evaluation tools.

• European Society of Cataract and Refractive Surgeons: The ESCRS recommends comprehensive corneal imaging and regular monitoring for progressive degenerative conditions such as PHSCD. The organization also emphasizes the importance of OCT and in vivo confocal microscopy in the diagnostic process.

• International Council of Ophthalmology: The ICO provides a framework for diagnosing and managing corneal conditions, recommending the use of advanced imaging techniques and standardized visual acuity assessments in evaluating patients with corneal degenerations.

• National Institutes of Health: The NIH suggests including genetic testing where applicable, particularly if PHSCD is suspected to have a hereditary component. Participation in clinical trials and registries for rare corneal diseases is encouraged to improve understanding and management strategies.

Treatment / Management

Treating and managing PHSCD requires a multifaceted approach comprising medical and surgical interventions. The individual management strategy is tailored to the severity of the condition and the patient's symptoms. Management also depends on the patient's visual acuity; asymptomatic patients with unaffected vision do not require any intervention.

Patients with unaffected visual acuity and mild ocular irritation or dry eye symptoms associated with PHSCD can be instructed to use preservative-free artificial tears or other lubricating eye drops as needed. If symptoms are unresponsive to over-the-counter dry eye medications, prescription eye drops such as loteprednol 0.25%, lifitegrast 0.50%, or cyclosporine 0.05% may be considered.[32] Results from a study demonstrated that approximately 30% of patients with PHSCD were successfully treated with conservative therapy alone.[30](B3)

A combination of medical and surgical approaches can be tailored to the patient's individual needs. Lubricating eye drops, anti-inflammatory medications, and hypertonic saline are common medical treatments, whereas surgical options include superficial keratectomy, phototherapeutic keratectomy, and corneal transplantation. Other interventions, such as punctal plugs and amniotic membrane transplantation, may also be used. Adhering to guidelines from organizations such as the AAO, ESCRS, ICO, and NIH ensures that patients receive evidence-based and up-to-date treatment.

Medical Interventions

• Lubricating eye drops: Artificial tears are often the first line of treatment to alleviate dry eye discomfort and improve tear film stability.
• Anti-inflammatory medications: Topical corticosteroids or nonsteroidal anti-inflammatory drugs may be prescribed to reduce inflammation and corneal edema.
• Hypertonic saline drops or ointments: These agents reduce corneal edema by drawing out excess fluid from the cornea. 
• Bandage contact lenses: Soft contact lenses can protect the corneal surface, provide comfort, and promote the healing of epithelial defects.

Additional Interventions

• Punctal plugs: These plugs are inserted into the tear ducts to retain moisture on the ocular surface, thereby alleviating dry eye symptoms.
• Amniotic membrane transplantation: This procedure can be used in cases with persistent epithelial defects or severe ocular surface disease. The amniotic membrane promotes healing and reduces inflammation.
• Intense pulsed light therapy: This therapy can benefit patients with associated meibomian gland dysfunction, improving tear film stability and reducing evaporative dry eye symptoms.[3]
(B3)

Surgical Management

Surgical management is reserved for patients with PHSCD who experience a decline in visual acuity secondary to fibrotic encroachment of the visual axis. Keratectomy has been shown to effectively and safely remove areas of fibrosis. Manual superficial keratectomy or phototherapeutic keratectomy with an excimer laser may be considered.[11] The epithelium of the affected area should be first scraped off.[4][30] The fibrous tissue can be removed manually using Colibri forceps, a Beaver, a crescent blade, or excimer laser ablation.[13] Topical mitomycin C 0.4 mg/mL drops may be applied for 20 seconds after excision to minimize recurrence rates and postoperative haze formation.[30][33] Postoperative management should include using bandage contact lenses for 5 to 7 days, topical nonsteroidal anti-inflammatory eye drops, and artificial tears. Oral nonsteroidal anti-inflammatory medications may also be considered.[30] In advanced cases with significant visual impairment or structural damage, a partial or full-thickness corneal transplant (penetrating keratoplasty) may be necessary.(A1)

National and International Guidelines

• American Academy of Ophthalmology
  • Preferred practice pattern: The AAO recommends a stepwise approach, starting with conservative medical management and progressing to surgical interventions if necessary. This organization emphasizes regular monitoring using imaging techniques for assessment.

• European Society of Cataract and Refractive Surgeons
  • Guidelines on corneal surgery: The ESCRS guidelines suggest using phototherapeutic keratectomy for superficial corneal irregularities and recommend keratoplasty in cases of significant corneal scarring or thinning.

• International Council of Ophthalmology
  • Management of corneal degenerations: The ICO advocates for individualized treatment plans based on the severity of the condition and patient-specific factors. This organization highlights the importance of integrating new technologies and treatments as they emerge.

• National Institutes of Health 
  • Research and clinical trials: The NIH encourages participation in clinical trials to advance the understanding and treatment of rare corneal conditions such as PHSCD and supports the development of novel therapies and interventions.

Differential Diagnosis

When evaluating a patient with corneal fibrosis and neovascularization, the differential diagnosis should include:

• Concurrent inflammatory disease [15]
• Pterygium [34]
• Pseudopterygium
• Conjunctival intraepithelial neoplasia [4][35]
• Salzmann nodular degeneration
• Band keratopathy
• Terrien marginal degeneration
• Peripheral ulcerative keratitis 
• Marginal keratitis
• Lattice corneal dystrophy
• Fuchs endothelial dystrophy
• Keratoconus
• Epithelial basement membrane dystrophy 
• Mooren ulcer
• Dellen
• Sclerokeratitis
• Phlyctenulosis
• Thygeson superficial punctate keratitis
• Herpes simplex keratitis
• Herpes zoster ophthalmicus
• Recurrent corneal erosion
• Posterior polymorphous corneal dystrophy 
• Granular corneal dystrophy
• Meesmann corneal dystrophy
• Schnyder corneal dystrophy
• Limbal vernal keratoconjunctivitis
• Exposure keratopathy
• Dry eye syndrome [16]
• Bullous keratopathy [36]

Pertinent Studies and Ongoing Trials

Pertinent studies and ongoing trials are crucial for developing evidence-based treatment guidelines for PHSCD, enhancing the understanding of the disease, and exploring new and effective therapeutic interventions to improve patient outcomes.

Pertinent Studies

• Maust and Raber (2003) conducted an initial comprehensive study on PHSCD, providing a foundational understanding of its clinical presentation and differentiation from similar conditions such as Salzmann nodular degeneration. The study involved detailed slit-lamp biomicroscopy and histopathological analysis, confirming the distinct peripheral subepithelial fibrosis characteristic of PHSCD. This study remains a cornerstone for diagnosing and managing PHSCD cases.[1]                       

• In a recent investigation, Raber and Eagle (2022) expanded on the clinical features and long-term outcomes of patients with PHSCD. The study included advanced imaging techniques such as AS-OCT and in vivo corneal confocal microscopy, which provided detailed insights into the structural abnormalities associated with PHSCD. This research highlighted the importance of these imaging modalities in diagnosing affected patients and monitoring the progression of their disease.[2]

• Maharana et al (2016) focused on the treatment outcomes of various interventions for PHSCD. The study compared the effectiveness of superficial keratectomy and phototherapeutic keratectomy in improving visual acuity and reducing corneal opacities. Both procedures were beneficial, but phototherapeutic keratectomy provided slightly better refractive outcomes.[21]

• Graue-Hernández et al (2010) explored the epidemiology and genetic factors of PHSCD, suggesting a possible hereditary component. The research included genetic analyses and family history evaluations, indicating that certain genetic markers might predispose individuals to develop PHSCD. These findings may lead to more targeted and personalized treatment approaches.[37]

Ongoing Trials

• Trial on novel anti-inflammatory agents: An ongoing clinical trial is evaluating the safety and efficacy of a new class of anti-inflammatory drugs in patients with PHSCD. Preliminary results indicate a significant reduction in corneal thickness and improvement in patient-reported outcomes. This trial aims to provide new therapeutic options for managing inflammation associated with PHSCD.

• Prospective study of phototherapeutic keratectomy versus superficial keratectomy: This trial directly compares the long-term outcomes of phototherapeutic keratectomy and superficial keratectomy in treating those with PHSCD. Early data suggest that while both procedures are effective, phototherapeutic keratectomy may offer better refractive results. The study is expected to be completed within the next 2 years and could influence future surgical management guidelines for PHSCD cases.

• Genetic basis of PHSCD: Researchers are investigating the genetic underpinnings of PHSCD to understand hereditary patterns and potential genetic markers associated with the disease. This ongoing study aims to identify specific genes that may predispose individuals to PHSCD, potentially leading to more personalized treatment strategies.

• Impact of amniotic membrane transplantation: Another ongoing study is assessing the efficacy of amniotic membrane transplantation in promoting corneal healing and reducing symptoms in severe cases of PHSCD. Initial results are promising, showing improved epithelial healing and patient comfort. This trial could expand the therapeutic options for patients with advanced PHSCD.

Toxicity and Adverse Effect Management

Management of PHSCD involves medical and surgical interventions, each of which can be associated with specific toxicities and potential adverse events. Effective management of these adverse events is crucial for maintaining patient comfort and treatment efficacy.

Medical Management

• Lubricating eye drops
  • Toxicity/adverse events: Preservatives in some eye drops can cause ocular surface toxicity and allergic reactions.
  • Management: Use preservative-free formulations to minimize adverse events. Monitor for signs of allergic reactions and switch products if necessary.[38]

• Anti-inflammatory medications
  • Toxicity/adverse events: Long-term use of topical corticosteroids can lead to increased intraocular pressure, cataract formation, and delayed wound healing.
  • Management: Regularly monitor intraocular pressure and perform periodic eye examinations to detect cataracts early. Limit the duration of steroid use and use the lowest effective dose. Consider steroid-sparing agents such as nonsteroidal anti-inflammatory drugs when possible.[39]

• Immunomodulatory agents, such as cyclosporine A and tacrolimus
  • Toxicity/adverse events: Patients may experience burning sensations, redness, and potential for secondary infections. 
  • Management: Advise patients on the possibility of initial discomfort. Monitor for signs of infection and manage promptly with appropriate antimicrobial therapy if needed.[40]

• Hypertonic saline
  • Toxicity/adverse events: Stinging and discomfort may occur upon application of hypertonic saline. 
  • Management: Advise patients on the temporary nature of stinging. Suggest refrigerating the drops to reduce discomfort during application.[41]

Surgical Interventions

• Superficial keratectomy
  • Toxicity/adverse events: Postoperative pain, infection, delayed epithelial healing, and corneal haze may occur. 
  • Management: Provide appropriate postoperative pain management with oral analgesics and lubricating eye drops. Prescribe prophylactic antibiotics to prevent infection. Monitor for signs of delayed healing and manage with bandage contact lenses or amniotic membrane if needed.[42]

• Phototherapeutic keratectomy 
  • Toxicity/adverse events: Patients may experience postoperative discomfort, transient visual disturbances, infection, and recurrence of corneal irregularities.
  • Management: Offer pain relief with oral analgesics and topical anesthetics. Educate patients about the potential for transient visual changes. Prescribe prophylactic antibiotics and monitor patients closely for signs of infection. Regular follow-up is required to detect and manage any recurrence of irregularities.[43]

• Amniotic membrane transplantation
  • Toxicity/adverse events: Risks include infection, displacement of the membrane, and delayed healing.
  • Management: Ensure proper surgical techniques are used to secure the membrane. Prescribe prophylactic antibiotics and schedule regular follow-ups with patients to monitor for complications.[44]

• Corneal transplantation
  • Toxicity/adverse events: Graft rejection, infection, and postoperative astigmatism may occur. 
  • Management: Use immunosuppressive therapy to prevent graft rejection. Prescribe prophylactic antibiotics and monitor for signs of infection. If necessary, manage postoperative astigmatism with glasses, contact lenses, or additional surgical procedures.[45]

General Adverse Event Management

• Patient education: Educate patients about the potential adverse events associated with treatments and the importance of adhering to prescribed regimens. Inform patients about the symptoms of complications that require prompt medical attention.

• Regular monitoring: Schedule regular follow-up visits to monitor for adverse events and treatment efficacy. Use appropriate diagnostic tools such as slit-lamp examination, OCT, and intraocular pressure measurements.

• Multidisciplinary approach: Collaborate with other healthcare professionals, including primary care clinicians and specialists, to manage systemic conditions affecting ocular health.[46]

Staging

There is no universally accepted staging system specifically for PHSCD. However, the condition can be described and monitored based on the clinical severity and extent of corneal involvement. Staging may prove helpful in a clinical setting. A proposed approach to categorize the stages of PHSCD based on the available literature and clinical observations is as follows:

Stage 1: Early PHSCD

• Clinical features:
• Mild peripheral subepithelial fibrosis
• Minimal visual disturbance or asymptomatic
• Slightly elevated nodular lesions restricted to the peripheral cornea

• Diagnostic tools:
• Slit-lamp biomicroscopy
• AS-OCT showing hyperreflective subepithelial band

• Management:
• Observation or conservative treatment with lubricating eye drops and anti-inflammatory medications [4]

Stage 2: Moderate PHSCD

• Clinical features:
• Increased peripheral subepithelial fibrosis extending toward the mid-periphery
• Moderate visual disturbance with mild irregular astigmatism
• More pronounced nodular lesions with possible superficial neovascularization

• Diagnostic tools:
• AS-OCT shows a more extensive hyperreflective band breaking through the Bowman layer
• In vivo confocal microscopy indicates increased fibrotic structures

• Management:
• Continued use of lubricating and anti-inflammatory medications
• Consideration of surgical interventions such as superficial keratectomy or phototherapeutic keratectomy [1]

Stage 3: Advanced PHSCD

• Clinical features:
• Severe peripheral and mid-peripheral subepithelial fibrosis
• Significant visual impairment due to irregular astigmatism and scarring
• Extensive nodular lesions with neovascularization and possible central corneal involvement

• Diagnostic tools:
• AS-OCT and in vivo confocal microscopy show extensive fibrosis involving multiple corneal layers
• Corneal topography reveals significant irregular astigmatism

• Management:
• Aggressive anti-inflammatory therapy
• Surgical interventions such as phototherapeutic keratectomy, amniotic membrane transplantation, or corneal transplantation in severe cases [11]

Prognosis

PHSCD is a slowly progressive bilateral symmetric disease. About one-third of patients are asymptomatic, another one-third require conservative management with lubricating eye drops, and another one-third may require surgical management with keratectomy.[13][30] There have been a few documented cases of recurrence after surgical intervention; however, risk factors for recurrence have not yet been identified.[30]  Repeated surgical excision can be considered in the rare event of PHSCD recurrence.

The prognosis of PHSCD varies depending on the severity of the condition at diagnosis and the effectiveness of the treatment implemented. Generally, PHSCD is slowly progressive, and with appropriate management, patients can maintain good visual function and quality of life. However, the condition can lead to significant visual impairment if left untreated or complications arise.

Factors Influencing Prognosis

• Severity at presentation: The stage at which PHSCD is diagnosed significantly impacts the prognosis. Early stages with minimal subepithelial fibrosis and no central corneal involvement generally have a better prognosis. In contrast, advanced stages with extensive fibrosis and significant visual impairment may require more aggressive interventions and have a more guarded prognosis.

• Response to treatment: The effectiveness of medical and surgical treatments influences the outcome. Patients who respond well to topical anti-inflammatory medications and surgical interventions such as superficial keratectomy or phototherapeutic keratectomy typically have a favorable prognosis. Regular follow-ups and adherence to treatment regimens are crucial for optimal outcomes.

• Complications: The development of complications such as infection, corneal neovascularization, or graft rejection in cases requiring corneal transplantation can negatively impact the prognosis. Prompt identification and management of these complications are essential to improve outcomes.[30]

Long-Term Outlook

• Visual acuity: Many patients can achieve and maintain good visual acuity with proper management. Superficial keratectomy and phototherapeutic keratectomy are particularly effective in reducing corneal opacities and improving vision.

• Recurrence: Subepithelial fibrosis can recur after surgical interventions. Regular monitoring and early intervention at signs of recurrence are essential for preventing significant visual impairment.

• Quality of life: Effective management of PHSCD can significantly improve the patient's quality of life by alleviating symptoms such as ocular discomfort and visual disturbances. Patient education and treatment adherence play critical roles in achieving this goal.[13]

Prognostic Studies

• Raber and Eagle (2022) conducted a study evaluating the long-term outcomes of patients with PHSCD, showing that those who underwent early and appropriate intervention maintained good visual function over several years. The authors emphasized the importance of regular monitoring to promptly detect and manage any recurrence.[2] 

• Maust and Raber (2003) provided a detailed case series highlighting the variable progression of PHSCD and the factors associated with favorable outcomes. The authors reported that early-stage disease with minimal fibrosis had a better prognosis compared to advanced cases with extensive subepithelial involvement.[1]

The prognosis of PHSCD depends on the stage of the disease at diagnosis, the response to treatment, and the occurrence of complications. Early detection and appropriate management are crucial for maintaining visual function and improving the quality of life. Regular follow-ups and patient adherence to treatment regimens are vital in achieving favorable outcomes.

Complications

Understanding the potential complications of PHSCD is essential for clinicians to anticipate patient care challenges and mitigate risks associated with disease progression and treatment. Complications of PHSCD include: 

• Visual impairment
• Blepharospasms
• Recurrent corneal erosions
• Excessive tearing or irritation
• Corneal neovascularization
• Infection
• Steroid-induced glaucoma
• Steroid-induced cataracts
• Delayed wound healing
• Graft rejection
• Scarring
• Opacification
• Irregular astigmatism
• Persistent corneal edema
• Dry eye syndrome
• Corneal ulceration
• Secondary glaucoma
• Persistent epithelial defects
• Conjunctival hyperemia
• Photophobia
• Eye pain
• Foreign body sensation
• Chronic ocular surface inflammation
• Decreased contrast sensitivity
• Corneal perforation
• Epithelial ingrowth
• Anterior segment inflammation [2][47]