Superior Keratoconus

Etiology

The exact etiology of superior keratoconus is not well understood. However, several risk factors and associated conditions have been identified, including eye rubbing, blepharoptosis, and connective tissue disorders like Ehlers-Danlos, Down, and Marfan syndromes.[15] Superior keratoconus is also linked to atopy.[16] However, this association is highly controversial, as superior keratoconus in patients with atopy may be largely due to eye rubbing in response to allergic conjunctivitis. These risk factors are similar to those of general keratoconus, but their relationship with superior keratoconus remains undetermined due to the small number of confirmed cases.

Like other forms of keratoconus, the etiology of superior keratoconus is multifactorial, involving a combination of genetic, environmental, and biochemical factors. Understanding the causes of superior keratoconus is essential for early diagnosis, management, and potential prevention strategies.

Genetic Factors

Superior keratoconus shows evidence of a hereditary component, often appearing in individuals with a family history of the disease. Research has identified several genetic loci and specific genes that contribute to its development, highlighting a complex genetic basis.

Hereditary component

Keratoconus often runs in families, suggesting a genetic predisposition. Multiple studies have identified various genetic loci associated with the disease, indicating a polygenic inheritance pattern.[17] Specific genes such as VSX1, SOD1, and ZEB1 have been implicated in the development of keratoconus, although no single gene mutation has been identified as the primary cause.

Genetic syndromes

Superior keratoconus, like other forms, is more prevalent in individuals with certain genetic disorders such as Down, Marfan, and Ehlers-Danlos syndromes. These conditions are characterized by connective tissue abnormalities that may predispose individuals to corneal ectasia.

Environmental Factors

Environmental factors play a significant role in the development and progression of superior keratoconus. External influences, such as mechanical trauma and allergic conditions, can exacerbate corneal weakening and contribute to the disease.

Eye rubbing

Chronic eye rubbing is strongly associated with the development and progression of keratoconus. The mechanical trauma from repeated rubbing can lead to microtrauma and weakening of the corneal structure.[18]

Atopy and allergies

Individuals with atopic conditions such as asthma, eczema, and allergic conjunctivitis are at increased risk of developing keratoconus. Chronic inflammation and rubbing due to itching may contribute to corneal weakening.[19]

Biochemical Factors

Biochemical factors significantly influence the development of superior keratoconus through disruptions in the corneal structure. Enzymatic activity imbalances and increased oxidative stress can compromise corneal integrity and contribute to disease progression.

Enzymatic imbalance

An imbalance between proteolytic enzymes and their inhibitors in the corneal stroma has been proposed as a contributing factor. Increased activity of matrix metalloproteinases (MMPs) and decreased levels of tissue inhibitors of metalloproteinases (TIMPs) can lead to extracellular matrix degradation, resulting in corneal thinning and ectasia.[20]

Oxidative stress

Increased oxidative stress and decreased antioxidant defenses in the cornea are believed to play a role in the pathogenesis of keratoconus. Oxidative damage to corneal cells and extracellular matrix components can weaken the cornea and predispose it to deformation.[21]

Mechanical Factors: Biomechanical Properties

Abnormal corneal biomechanical properties, such as reduced corneal stiffness and altered collagen cross-linking, can contribute to the development of keratoconus. These changes make the cornea more susceptible to deformation under normal intraocular pressure.[22]

Hormonal Factors

Hormonal changes, particularly during puberty and pregnancy, may influence the progression of keratoconus. Hormonal fluctuations can affect the biomechanical properties of the cornea, potentially exacerbating ectasia.[23]

The etiology of superior keratoconus is complex and multifactorial, involving genetic predisposition, environmental influences, biochemical imbalances, mechanical factors, and possibly hormonal changes. Understanding these factors can help identify individuals at risk for developing superior keratoconus and initiate early intervention.

Epidemiology

The incidence of isolated superior keratoconus is largely unknown and has not been specifically reported due to its extreme rarity. However, the disease is thought to account for less than 1% of all confirmed keratoconus cases. The incidence rate of general keratoconus is thought to range from 1.5 to 25 per 100,000 persons per year, affecting all ethnicities and sexes. The current estimated prevalence rate is thought to be between 0.2 and 4,790 per 100,000 persons per year.[24] Most superior keratoconus cases are undiagnosed until the later stages due to their initially subclinical presentation. 

Superior keratoconus is a rare variant of keratoconus characterized by corneal thinning and steepening, primarily in the superior cornea. The epidemiology of superior keratoconus resembles that of general keratoconus but includes some distinct aspects due to its unusual presentation.

General Epidemiology of Keratoconus

The prevalence of keratoconus varies widely across different populations. The condition's presentation and demographic patterns can offer insights into its broader epidemiological profile.

Prevalence

Studies estimate the prevalence of keratoconus to range from 50 to 230 per 100,000 in the general population.[25] The prevalence of keratoconus is approximately 54.5 per 100,000 individuals in the United States.[26] Higher prevalence rates have been reported in certain ethnic groups, such as people of Middle Eastern, South Asian, and African descent.[27]

Age distribution

Keratoconus typically presents during adolescence and early adulthood, with the age of onset commonly between 10 and 25 years. The condition progresses over 10 to 20 years before stabilizing.[28] The disease is often diagnosed in the 2nd and 3rd decades of life, corresponding to the period of rapid corneal changes.[29]

Sex distribution

Keratoconus has a slight male predominance. The male-to-female ratio varies in different studies but is generally around 1.5:1.

Specific Epidemiology of Superior Keratoconus

Superior keratoconus is a rarer form of keratoconus with limited prevalence data. This disorder's geographical, age, and sex distribution generally align with the broader patterns observed in keratoconus.

Frequency

Superior keratoconus is less common than the typical inferior form. Precise prevalence data for superior keratoconus are limited due to its rarity and the challenge of differentiating it from other corneal ectatic disorders.[30] Case series and reports indicate that superior keratoconus constitutes a small percentage of all keratoconus cases, with some estimates suggesting it accounts for less than 5% of all cases.

Geographical distribution

Like general keratoconus, superior keratoconus does not show a significant geographical preference. However, the higher prevalence of keratoconus in certain ethnic groups may also be reflected in the distribution of superior keratoconus within those populations.[31]

Age and sex distribution

The age of onset and progression pattern of superior keratoconus are similar to those of typical keratoconus, with onset in the 2nd to 3rd decades of life. The male predominance observed in general keratoconus is also seen in superior keratoconus, although specific data on sex distribution are scarce.[32]

Global Perspective

Studies from various parts of the world, including the Middle East, Asia, and Africa, have reported higher rates of keratoconus. These rates reflect genetic and environmental factors that may also influence the prevalence of superior keratoconus in these regions.[33]

By understanding the epidemiological characteristics of superior keratoconus, healthcare providers can better identify at-risk populations and implement early screening and intervention strategies to manage this rare corneal disorder effectively.

Pathophysiology

The proposed pathophysiological mechanisms of superior keratoconus are thought to be the same as general keratoconus, although not entirely understood. Many proteins, such as TGF-β1, collagen type IV, secreted protein acidic and cysteine-rich (SPARC), wingless-related integration site (Wnt), Hedgehog (Hh), and cellular adhesion molecules, are believed to be dysregulated in patients with superior keratoconus.[34] These abnormally expressed proteins may lead to structural changes in the cornea via keratocyte apoptosis and stromal necrosis.

Dysregulation of oxidative stress markers and antioxidants may also play a significant role in the pathogenesis of superior keratoconus. Corneal stromal thinning and degeneration may be caused by decreased concentrations of antioxidants such as aldehyde/NADPH dehydrogenase, lactoferrin, transferrin, and albumin and increased concentrations of reactive oxidative stress markers such as reactive oxygen species, nitrogen, and malondialdehyde in the stroma. Additionally, increased levels of lysosomal enzymes have been found in the stromal keratocytes of patients with keratoconus, potentially explaining damage seen in the anterior stromal membrane. Physical stresses, such as increased intraocular pressure and eye rubbing, may exacerbate this degradation.[35]

Histopathology

Histopathological findings of superior keratoconus may demonstrate both stromal and epithelial thinning, predominantly in the superior cornea. Breaks in the Bowman layer, Descemet membrane, or both may also be observed. Panstromal scarring and Descemet membrane rupture with subsequent hydrops may be seen in the later stages of superior keratoconus.[36]

Histopathological examination of corneal tissue in the superior keratoconus reveals a range of microscopic changes that reflect structural abnormalities and disease progression. These findings help understand the underlying pathophysiology and differentiate superior keratoconus from other ectatic corneal disorders.

Epithelial Changes

The corneal epithelium in keratoconus often shows thinning and irregularity. This disruption can lead to breaks in the Bowman layer, contributing to the characteristic corneal steepening. Irregularities in the epithelium's basal cell layer are frequently observed, indicating chronic stress and damage.[37]

Bowman Layer Breaks and Scarring

The Bowman layer often shows localized breaks and, in advanced cases, scarring. These breaks are significant as they contribute to corneal protrusion and the irregular astigmatism seen clinically.[38]

Stromal Changes

The stromal layer shows significant thinning, which is more pronounced in the superior part of the cornea. This thinning is a key feature that differentiates superior keratoconus from other forms of keratoconus.[39] The normally regular arrangement of collagen lamellae in the stroma becomes disrupted. Abnormal collagen fibrils appear interspersed, weakening the corneal structure.[40] Increased apoptosis of keratocytes, the cells responsible for maintaining the corneal stroma, is observed. This cell loss contributes to stromal thinning and weakening.[41]

Changes in the Descemet Membrane and Endothelium

Clinically visible vertical stress lines in the Descemet membrane called "Vogt striae" arise, correlating with breaks or folds seen histologically. The endothelium is generally spared in early keratoconus. However, advanced cases may show endothelial cell loss and pleomorphism, reflecting the overall corneal stress.[42]

Presence of Inflammatory Cells

Keratoconus is primarily a noninflammatory disorder. However, mild infiltration of inflammatory cells is sometimes observed, particularly in areas of significant tissue damage or scarring.[43]

Significance of Histopathological Findings

Histopathological examination provides crucial insights into the progression of superior keratoconus. The observed changes, such as stromal thinning, collagen disorganization, and keratocyte apoptosis, highlight the disease's degenerative nature. These findings support the clinical and imaging diagnoses and help differentiate superior keratoconus from other corneal pathologies like pellucid marginal degeneration or keratoglobus. Understanding the histopathology of superior keratoconus aids in developing targeted treatments aimed at strengthening the corneal structure, such as CXL, and provides the basis for ongoing research into the pathophysiology of corneal ectatic disorders.

History and Physical

Patient Presentation

Patients with superior keratoconus often present with progressively worsening and fluctuating visual acuity with associated glare, halos, and photophobia. A thorough medical history gathering may reveal atopy, eye rubbing, or a family history of keratoconus. External examination of the patient's eyes may reveal abnormal protrusion and an inverse Munson sign, characterized by a V-shaped indentation of the upper eyelid during upgaze (see Image. Keratoconus).

Onset and progression

Symptoms typically begin in the 2nd to 3rd decade of life, although they can start earlier in some cases. Superior keratoconus gradually worsens over time, with periods of relative stability interspersed with episodes of rapid deterioration.

Family history

A positive family history of keratoconus or other ectatic corneal disorders may be present, suggesting a genetic component.[44] This information is crucial during history-taking to identify individuals at higher risk and to guide further diagnostic evaluation.

Associated conditions

Frequent eye rubbing, often due to associated conditions such as allergies or atopy, may be a contributing factor. Conditions like Down syndrome and connective tissue disorders like Marfan and Ehlers-Danlos syndromes may be associated with keratoconus.[45]

Physical Examination Findings

Slit-lamp biomicroscopy may show normal findings in subclinical superior keratoconus.[46] Findings in the later stages of superior keratoconus may include the following:

• Superior central and paracentral corneal thinning and superior steepening
• Superior Vogt striae or vertical stress lines formed by the compression of the Descement membrane
• Partial breaks in the Bowman or Descemet membrane
• Complete or partial Fleischer rings or iron deposits in the basal corneal epithelial cells, visualized as a brown or yellow ring using a cobalt blue filter attached to the slit-lamp [47]
• Rizutti's sign, which is a bright reflection of the nasal limbal area when light shines on the temporal limbus
• Acute corneal hydrops with subsequent stromal scarring [48]
• Scissoring reflex on retinoscopy, indicating irregular astigmatism [49]
• Corneal topography reveals superior corneal steepening and asymmetry, which are key diagnostic features distinguishing superior keratoconus from other variants.[50]
• The posterior segment is typically normal unless complications develop from advanced disease.

By taking a thorough history and performing a detailed physical examination, including specialized diagnostic tests, clinicians can accurately diagnose superior keratoconus and differentiate it from other corneal conditions. This comprehensive approach ensures appropriate disease management and monitoring to prevent significant visual impairment.

Evaluation

The evaluation of superior keratoconus involves a combination of clinical examination, advanced imaging techniques, and other diagnostic tests. These methods are used to accurately assess disease extent, monitor progression, and guide treatment decisions.

Clinical Examination

The initial diagnosis of superior keratoconus involves measuring the patient's refraction. Additionally, standard visual acuity tests, including testing with and without corrective lenses, determine the level of vision impairment.

Slit Lamp Biomicroscopy

Slit-lamp biomicroscopy is used to assess for clinical signs of superior keratoconus, as described above. This modality allows for a detailed examination of the corneal structure and identification of key features.

Corneal Topography

Corneal topography is a diagnostic method used to screen and evaluate patients with superior keratoconus. Findings include superior central and paracentral corneal thinning with superior steepening. The S-I ratio, a value comparing the average power difference between the cornea's superior and inferior hemispheres, may be between 1.4 and 1.8 in patients with superior keratoconus.[51] Changes in the cornea's anterior elevation may be 20 µm or greater. Changes in the cornea's posterior elevation can be 50 µm or greater.[52] Corneal pachymetry at the thinnest point of the cornea may be 495 µm or less. Corneal topographical patterns may include an asymmetric bowtie with or without superior steening, skewed radial axes, and an inferior flat area of decreased steepening.

Anterior Segment Optical Coherence Tomography 

Anterior segment optical coherence tomography (OCT) is useful as a pachymetry tool in revealing corneal thickness asymmetries that may be masked in patients with superior keratoconus due to epithelial remodeling. Fourier-domain OCT devices are also useful in assessing corneal epithelial thickness distribution changes.[53]

Retinoscopy

Retinoscopy is a highly sensitive and reliable test for detecting keratoconus, including the early stages of the disease. Findings include a scissoring reflex, characterized by 2 light bands moving toward and away from each other.[54]

Corneal Tomography

Corneal tomography provides a 3-dimensional image of the cornea, measuring both anterior and posterior surfaces as well as corneal thickness. Techniques like Scheimpflug imaging and optical coherence tomography (OCT) are commonly used. Tomography is essential for detecting early keratoconus and subclinical cases, and various ophthalmology societies recommend it for comprehensive assessment.[55]

Pachymetry

Pachymetry measures the cornea's thickness, which is crucial for assessing the extent of corneal thinning and determining eligibility for treatments like CXL. Regular pachymetric assessments are recommended to monitor disease progression and treatment response.[56]

Biomechanical Assessment

Devices such as the Ocular Response Analyzer (ORA) and CorVis ST measure corneal biomechanical properties, providing additional information about corneal rigidity and susceptibility to ectasia. These assessments are useful adjuncts to topography and tomography, aiding in early diagnosis and risk stratification.[57]

Refraction and Keratometry

Detailed refraction tests are used to measure the degree of myopia or astigmatism. Keratometry is used to measure the curvature of the cornea. These modalities are essential for documenting changes over time. Routine refraction and keratometry are part of the standard evaluation protocol for patients with keratoconus.[58]

Genetic Testing

Genetic testing can identify mutations associated with keratoconus, providing insights into familial patterns and risk factors. While not routine, genetic testing may be recommended in cases with a strong family history or atypical presentation.[59]

Other Diagnostics

Endothelial cell density and morphology may also be assessed. These attributes may be affected in advanced keratoconus or after corneal surgery. Specular microscopy is recommended for preoperative assessment and postoperative monitoring in patients with keratoconus undergoing surgical interventions.[60]

By following these evaluation protocols and guidelines, healthcare providers can accurately diagnose superior keratoconus, monitor its progression, and tailor treatment plans to patients' needs, improving outcomes and quality of life.

Treatment / Management

The treatment options for superior keratoconus are similar to those of general keratoconus. Management options depend on the disease stage and progression.[61] Management is also classified into nonsurgical and surgical techniques. (B3)

Nonsurgical Management

Nonsurgical management of superior keratoconus focuses on preserving and improving visual acuity through conservative corrective measures. Treatment strategies vary depending on the severity of the condition, ranging from glasses and contact lenses to specialized scleral lenses.

Mild superior keratoconus

Treatment focuses on maintaining adequate visual acuity for the patient, usually in the form of prescribing glasses. Hard contact lenses such as RGP or scleral lenses may be considered based on patient preference.[62]

Moderate superior keratoconus

Patients at this stage typically use contact lenses to correct their vision. Options may include RGP lenses, which correct corneal irregularities. However, patients may find these lenses intolerable, and they are usually not prescribed for individuals currently or previously with corneal scarring. Scleral lenses are being used now for patients with moderate keratoconus, as these lenses allow a tear vault to form in the space between the cornea and the lens, aiding in correcting irregular astigmatism and refractive errors. Scleral lenses also have a lower risk of dislocation on the cornea and are found to be more comfortable by patients.[63](A1)

Severe superior keratoconus

Patients with severe keratoconus are at high risk of corneal stromal scarring due to the likelihood of experiencing episodes of acute corneal hydrops. Scleral lenses are the preferred treatment option for these patients.

Surgical Management

Surgical management of superior keratoconus involves various procedures aimed at stabilizing the cornea and improving visual acuity. Treatment options range from cross-linking and corneal transplants to specialized techniques like DALK and intrastromal corneal ring segments (ICRSs).

Cross-linking

This procedure is indicated for progressive keratoconus and promotes the strengthening and stability of the cornea's collagen fibrils. Cross-linking involves removing a portion of the central epithelium and administering riboflavin solution drops. This step is followed by UV-A light exposure that activates riboflavin and generates reactive oxygen species to form covalent bonds between the collagen and proteoglycans in the cornea.[64] This procedure is often coupled with photorefractive keratectomy to aid in refractive correction.[65] Contraindications for this procedure include corneal thickness of less than 400 µm, prior or active herpetic eye infection, severe corneal scarring, certain autoimmune disorders, and severe ocular surface disease.

Penetrating keratoplasty

Corneal transplants are indicated when lenses are no longer effective in correcting visual acuity. Approximately 10% to 20% of patients with keratoconus will require a corneal transplant.[66] Penetrating keratoplasty (PKP) is a full-thickness transplant that involves removing all layers of the host cornea and replacing them with a healthy donor cornea. Patients typically achieve adequate visual acuity after surgery.

PKP may be indicated in patients with keratoconus and concurrent endothelial dysfunction or deep stromal scarring. Residual astigmatism after surgery may be corrected with contact lenses or other forms of refractive correction.[67] A known complication of PKP is graft rejection, so patients typically are treated with corticosteroids for a year or longer.[68] Contraindications include severe ocular surface disease, certain autoimmune disorders, very poor eyelid hygiene, severe corneal neovascularization, and various forms of ocular surface inflammation.

Deep anterior lamellar keratoplasty

DALK is a partial-thickness corneal transplant that replaces the host cornea's epithelium and anterior stroma. DALK offers faster visual recovery and a reduced risk of graft rejection and failure compared to PKP.[69] This procedure is preferred for patients without endothelial dysfunction. Contraindications are similar to those of PKP.[70](A1)

Intrastromal corneal ring segments

Small plastic rings are inserted into the stroma to flatten the cornea, improving visual acuity and reducing myopia. Notably, ICRS does not treat or slow the progression of keratoconus. The procedure is only useful for correcting visual acuity. Contraindications include a corneal thickness of less than 450 µm, corneal scarring, and the possibility of improving vision with contact lenses.

Other Interventions

Other nonsurgical approaches are available for managing superior keratoconus. These modalities include pharmacological treatments to control inflammation and visual rehabilitation techniques to enhance the quality of life for patients with significant visual impairment. Topical corticosteroids and nonsteroidal anti-inflammatory drugs may be used postoperatively to control inflammation and prevent complications.[71] For patients with significant visual impairment not correctable by surgery or contact lenses, low vision aids and rehabilitation services are essential to improving their quality of life.[72](A1)

Monitoring and Follow-Up

Regular follow-up is crucial for monitoring disease progression and treatment effectiveness. Advanced imaging techniques, such as corneal topography and OCT, assess corneal shape and thickness changes over time.[73]

Psychological Support

Living with a chronic condition like superior keratoconus can be challenging, and psychological support, including counseling and support groups, can help patients cope with the emotional and psychological impacts of the disease. By adhering to these guidelines and employing a multifaceted approach to treatment, healthcare providers can effectively manage superior keratoconus, improving visual outcomes and patients' quality of life.[74](A1)

Differential Diagnosis

Several differential diagnoses must be considered when evaluating a patient with corneal thinning, including the following:

• Corneal ectasia (iatrogenic)
• Terrien marginal degeneration
• Fuchs endothelial dystrophy 
• Contact lens warpage

Superior keratoconus, a keratoconus variant, also shares many clinical features with other corneal ectatic disorders and conditions that affect corneal curvature and thickness. Accurate diagnosis is crucial, and several other conditions must be considered and ruled out. Below are some of the key differential diagnoses.

Pellucid Marginal Degeneration

Pellucid marginal degeneration (PMD) is a bilateral, noninflammatory corneal thinning disorder characterized by a peripheral band of thinning, typically in the inferior cornea but occasionally affecting the superior cornea. PMD presents with a classic "kissing doves" or "crab-claw" pattern on corneal topography, which differs from the asymmetric, superior steepening seen in superior keratoconus.[75]

Keratoglobus

Keratoglobus is a rare ectatic disorder marked by diffuse, generalized corneal thinning, producing a globular shape. Unlike superior keratoconus, which shows localized superior thinning and steepening, keratoglobus affects the entire cornea, resulting in a more uniform, globular protrusion.[76]

Terrien Marginal Degeneration

Terrien marginal degeneration is a rare, slowly progressive thinning disorder that typically begins superiorly and progresses circumferentially. This condition is usually characterized by vascularization and lipid deposition at the leading edge of the thinning area, features not seen in superior keratoconus.[77]

Posterior Keratoconus

Posterior keratoconus is characterized by localized posterior corneal surface thinning, leading to an irregular posterior corneal curvature. This disorder primarily affects the posterior cornea, unlike the superior keratoconus, which involves anterior corneal thinning and steepening.

Contact Lens-Induced Corneal Warpage

Long-term use of rigid contact lenses may cause corneal shape changes that mimic ectatic disorders. Corneal warpage typically resolves after discontinuing contact lens use, and the topographic changes are usually symmetric, unlike the progressive nature of superior keratoconus.[78]

Post-Laser-Assisted In Situ Keratomileusis Ectasia

Laser-assisted in situ keratomileusis (LASIK) reshapes the cornea with a laser to correct vision and reduce the need for corrective lenses. Post-LASIK ectasia is a complication characterized by progressive corneal thinning and bulging. The history of refractive surgery and the location of ectasia corresponding to the LASIK flap help differentiate this condition from superior keratoconus.[79]

Corneal Dystrophies

Several corneal dystrophies, such as lattice and granular dystrophies, can cause corneal structural changes. These dystrophies typically present with distinct opacities or deposits within the corneal layers, visible on slit-lamp examination and not seen in keratoconus.[80]

Accurate diagnosis involves a thorough clinical examination, corneal topography, and tomography. Advanced imaging techniques, such as OCT and Scheimpflug imaging, can provide detailed maps of the corneal surface and thickness, aiding in differentiation. By considering these differential diagnoses, clinicians can more accurately diagnose superior keratoconus and implement appropriate management strategies to improve patient outcomes.

Pertinent Studies and Ongoing Trials

Hersh et al conducted a study titled "Corneal collagen crosslinking for keratoconus and corneal ectasia: one-year results," which evaluated the efficacy of CXL in patients with keratoconus and corneal ectasia. The results suggested significant corneal stabilization, with reduced progression of ectasia over one year, supporting the use of CXL as an effective treatment to halt the progression of superior keratoconus.[81]

Wittig-Silva et al conducted a randomized controlled trial of CXL in progressive keratoconus. The 3-year follow-up data from this trial showed sustained stabilization and improvement in corneal curvature, providing robust evidence for the long-term benefits of CXL in managing keratoconus, including superior keratoconus.[82]

Reinhart et al compared the outcomes of DALK with PKP in patients with keratoconus. The group's research revealed that DALK was a viable alternative to PKP, with fewer complications and better postoperative recovery, making it a recommended option for advanced superior keratoconus.[83]

Ongoing trials at the National Eye Institute and other research institutions continue to evaluate the long-term outcomes of various treatment modalities for superior keratoconus, including newer surgical techniques and genetic therapies. These studies aim to enhance understanding of the disease, improve diagnostic techniques, and develop more effective treatments, ultimately improving patient outcomes and quality of life for those with superior keratoconus.

Treatment Planning

Given the disease presentation and progression variability among patients, treatment planning for superior keratoconus involves a detailed and personalized approach. Below are the key components of treatment planning for superior keratoconus.

Diagnosis and Initial Assessment

• Comprehensive eye examination: Includes visual acuity tests, slit-lamp examination, and retinoscopy to evaluate the degree of corneal thinning and protrusion
• Corneal imaging: Advanced imaging techniques such as corneal topography and tomography are essential for detailed corneal surface mapping and staging the disease [84]

Nonsurgical Management

• Contact lenses: Customized contact lenses, including RGP and scleral lenses, are often the first line of treatment to improve visual acuity by providing a more regular refractive surface.
• Monitoring: Regular follow-up visits to monitor disease progression using corneal imaging and visual acuity tests. The frequency of visits may vary based on the severity and progression of the disease.[85]

Corneal Cross-Linking

• Indications: Recommended for patients with progressive keratoconus to strengthen corneal tissue and halt progression
• Procedure: CXL involves riboflavin application and subsequent exposure to UVA light. The total dose and duration are tailored to the patient's corneal thickness and curvature.
• Follow-up: Post-CXL monitoring includes regular check-ups to assess corneal stability and detect any adverse effects.[84]

Surgical Interventions

• ICRS
• Indications: Suitable for patients with moderate keratoconus and intolerant to contact lenses or have significant visual impairment
• Procedure: Insertion of plastic rings into the corneal stroma to flatten the cornea and improve vision
• Follow-up: Regular monitoring for complications such as infection or displacement of the rings.[86]
• Optical Penetrating Keratoplasty (OPK) vs DALK
• Indications: Considered for advanced cases with severe corneal scarring or thinning
• Procedure: Replacement of the damaged corneal tissue with donor tissue. The choice between therapeutic keratoplasty (TPK) and DALK depends on the depth of corneal involvement.
• Follow-up: Long-term follow-up is critical to monitor for graft rejection and ensure graft stability.[87]

Postoperative and Rehabilitation Care

• Medication adherence: Postsurgical patients are prescribed antibiotics and anti-inflammatory eye drops to prevent infection and reduce inflammation.
• Visual rehabilitation: Use of corrective lenses or visual aids to maximize postoperative visual outcomes.
• Psychological support: Counseling and support groups to help patients cope with the psychological impact of chronic eye disease.[88]

Advanced Imaging and Technology

Advanced imaging modalities include topography and tomography. These techniques provide detailed views of corneal structure, aiding in precise diagnosis and monitoring of keratoconus progression.[89]

Individualized Treatment Plans

• Personalized approach: Each patient's treatment plan is tailored based on the severity of keratoconus, rate of progression, and individual needs.
• Interdisciplinary collaboration: Coordination among ophthalmologists, corneal specialists, contact lens specialists, and other healthcare providers ensures comprehensive care.[90]

Healthcare providers can effectively manage superior keratoconus and improve patient outcomes by adopting a comprehensive and individualized approach to treatment planning.

Toxicity and Adverse Effect Management

Managing toxicity and adverse effects is critical to treating superior keratoconus, particularly given the various treatments involved, including medications, contact lenses, and surgical interventions. Below are key considerations and strategies for managing these issues.

Contact Lens-Related Complications

• Toxicity: Extended use of contact lenses, especially RGP and scleral lenses, can lead to corneal hypoxia, epithelial breakdown, and microbial keratitis. Management involves ensuring proper fitting and periodic evaluation of the lenses. Patients should be educated on proper lens hygiene and the importance of follow-up visits.

• Adverse effects: Common issues include discomfort, dry eye symptoms, and lens intolerance. Management involves using lubricating eye drops to alleviate dryness, taking breaks from lens-wearing to allow the cornea to recover, and, if necessary, switching to a different type of lens.[91]

Medication-Related Toxicity

• Corticosteroids: Topical corticosteroids are often used postsurgically to reduce inflammation, but prolonged use can cause elevated intraocular pressure and cataract formation. Management consists of monitoring intraocular pressure regularly and adjusting the dosage as necessary. Consider steroid-sparing agents if long-term treatment is required.

• Antibiotics: Long-term use of these medications can lead to resistance or toxicity. Management comprises using the lowest effective dose for the shortest duration possible. The patient should be regularly evaluated for signs of toxicity or resistance, and the treatment regimen should be adjusted accordingly.[92]

Corneal Cross-Linking Complications

• Toxicity: CXL involves the use of riboflavin and ultraviolet-A (UVA) light, which can cause corneal haze and endothelial cell damage if not performed correctly. Management involves ensuring strict adherence to the protocol to minimize UVA exposure. The cornea must be monitored postprocedure for any signs of haze or damage. Adjust treatment parameters based on individual corneal thickness.

• Adverse Effects: Pain, photophobia, and transient visual disturbances are common after CXL. Management consists of providing adequate pain relief and anti-inflammatory medications postprocedure. Educate patients about the expected temporary nature of these side effects.

Surgical Complications

• OPK and DALK: These procedures carry a risk of graft rejection and failure. Management involves implementing strict postoperative monitoring and immunosuppressive therapy as needed. Patients should be educated on the signs of rejection and the importance of early intervention.

• Adverse Effects: Infection, suture-related complications, and irregular astigmatism may arise. Management comprises prophylactic antibiotics to prevent infection, regular follow-up to remove sutures, and glasses or contact lenses to correct postoperative refraction errors.

Psychological Impact

The chronic nature of superior keratoconus and its impact on vision can lead to significant psychological stress, anxiety, and depression. Management involves providing psychological support and counseling. Referral to a mental health professional may be necessary for patients exhibiting significant distress.

By addressing these potential toxicities and adverse effects through vigilant monitoring, patient education, and timely intervention, healthcare providers can optimize the management of superior keratoconus and improve patient outcomes.[93]

Staging

Amsler-Krumeich Classification

Like other forms of keratoconus, superior keratoconus may be staged to assess the severity of the disease and guide treatment decisions. The Amsler-Krumeich classification is one of the most widely used staging systems for keratoconus and may also be applied to superior keratoconus.

Stage 1

• Findings: Slight central or paracentral inferior steepening, mild myopia, or astigmatism less than 5.00 diopters (D)
• Corneal thickness: Minimum thickness greater than 500 microns
• Clinical presentation: Often asymptomatic or mild visual disturbances
• Management: Regular monitoring, corrective lenses (glasses or contact lenses) [94]

Stage 2

• Findings: More pronounced inferior steepening, myopia, or astigmatism between 5.00 and 8.00 D.
• Corneal thickness: Minimum thickness between 400 and 500 microns
• Clinical presentation: Increased visual disturbances and need for more frequent changes in corrective lenses
• Management: Contact lenses (RGP or scleral lenses), CXL

Stage 3

• Findings: Severe inferior steepening, myopia, or astigmatism between 8.00 and 10.00 D, presence of corneal thinning and ectasia
• Corneal thickness: Minimum thickness between 200 and 400 microns
• Clinical presentation: Significant visual impairment, frequent changes in lens prescription, and possible corneal scarring
• Management: Contact lenses, CXL, consideration of surgical options such as ICRS or TPK

Stage 4

• Findings: Advanced inferior steepening, myopia, or astigmatism greater than 10.00 D, marked corneal thinning, and central scarring
• Corneal thickness: Minimum thickness of less than 200 microns
• Clinical presentation: Severe visual impairment, intolerance to contact lenses, significant corneal scarring
• Management: Surgical intervention, primarily TPK or DALK, with a potential need for corneal transplantation

Additional Considerations for Superior Keratoconus

• Topographic and tomographic analysis: Advanced imaging techniques such as corneal topography and tomography are essential for accurately staging superior keratoconus. These tools help assess the extent of corneal steepening, thinning, and asymmetry, which are critical for staging and treatment planning.[95]
• Clinical course and progression: Superior keratoconus may have a different progression pattern compared to classic keratoconus, often presenting with asymmetric and more localized superior involvement. Regular monitoring and early intervention are crucial to prevent significant visual impairment.
• Individualized treatment plans: The staging of superior keratoconus should guide individual treatment plans, taking into account the specific characteristics of the superior corneal involvement and the patient's overall ocular health.[96]

By utilizing the Amsler-Krumeich classification and incorporating advanced diagnostic tools, clinicians can effectively stage superior keratoconus and implement appropriate management strategies to optimize patient outcomes.

Prognosis

The prognosis of superior keratoconus is similar to that of general keratoconus. The condition is characterized by progressive corneal thinning and worsening of visual acuity. Approximately 10% to 20% of patients will require some form of corneal transplant during the course of the disease.

The prognosis of superior keratoconus varies depending on the stage of the disease at diagnosis, the rate of progression, and the effectiveness of the management strategies employed. Like other forms of keratoconus, superior keratoconus is a progressive condition that can lead to significant visual impairment if not properly managed.

Factors Influencing Prognosis

• Early detection and intervention: Early diagnosis through regular screenings and the use of advanced imaging techniques such as corneal topography can significantly improve the prognosis. Early intervention with treatments such as CXL can halt the progression of the disease and preserve vision.
• Treatment effectiveness: Treatment success plays a critical role in determining the prognosis. Treatments such as RGP and scleral lenses, CXL, and, in severe cases, OPK or DALK are essential in managing the condition and improving visual outcomes.[97]
• Stage at diagnosis: The stage of superior keratoconus at the time of diagnosis is a key determinant of prognosis. Patients diagnosed at an earlier stage generally have a better prognosis due to the availability of more effective treatment options to halt disease progression.
• Compliance with treatment: Patient adherence to prescribed treatments and follow-up schedules is crucial for achieving optimal outcomes. Noncompliance can lead to disease progression and poorer visual prognosis.[98]

Long-Term Prognosis

• Stable vision with treatment: With appropriate and timely treatment, many patients with superior keratoconus can achieve stable vision and maintain a good quality of life. CXL, in particular, has been shown to be effective in stabilizing the cornea and preventing further ectasia.
• Potential for visual rehabilitation: Even in advanced stages, surgical interventions such as TPK and DALK can restore significant visual function. However, these procedures carry risks such as graft rejection and require long-term follow-up.
• Risk of complications: Patients with superior keratoconus are at risk of complications such as corneal scarring, acute hydrops, and graft failure post-keratoplasty. These complications can adversely affect the prognosis and necessitate additional treatments.
• Genetic factors: Genetic predisposition may influence the prognosis. Patients with a family history of keratoconus may experience a more rapid progression and require more aggressive management.[99]

Overall Prognosis

The overall prognosis for superior keratoconus is generally favorable with early detection and appropriate management. Advances in diagnostic technologies and treatments have significantly improved the ability to manage this condition effectively. Regular monitoring and individualized treatment plans are essential to optimize visual outcomes and enhance the quality of life for patients with superior keratoconus.

Complications

Complications of superior keratoconus are similar to those of general keratoconus and can significantly impact visual acuity and quality of life. The primary complications associated with superior keratoconus are described below.

Progressive Corneal Thinning and Ectasia

The hallmark of keratoconus is progressive corneal thinning and bulging, which is more pronounced in the superior portion of superior keratoconus. This thinning can lead to significant visual distortion and impairment.[100]

Corneal Scarring

Scarring can occur as the cornea thins and becomes more irregular, particularly if the condition progresses to advanced stages. Corneal scarring can severely affect vision and may necessitate surgical intervention.[101]

Acute Corneal Hydrops

This condition is a sudden and severe complication characterized by the rupture of the Descemet membrane, leading to the influx of aqueous humor into the cornea. Acute corneal hydrops results in corneal swelling, pain, and a sudden decrease in vision.[102]

Contact Lens Intolerance

Many patients with superior keratoconus rely on RGP or scleral lenses for vision correction. However, the corneal shape may become too irregular as the disease progresses, making it difficult or impossible to fit contact lenses comfortably.

Graft Failure Post-Keratoplasty

Patients undergoing OPK or DALK have an increased risk of graft rejection or failure. This complication can occur due to immune reactions, infection, or improper healing.

Visual Disturbances

Patients with superior keratoconus often experience significant visual disturbances, including ghosting, glare, halos, and double vision. These symptoms can impair daily activities and reduce the overall quality of life.[103]

Psychological Impact

The chronic and progressive nature of superior keratoconus can lead to psychological stress and anxiety. Patients may experience frustration and depression due to the condition's impact on their vision and the limitations it imposes on their lifestyle.

Recurrent Corneal Infections

Due to compromised corneal integrity, patients with superior keratoconus are at an increased risk of recurrent corneal infections. The resulting inflammation can further complicate the condition and lead to additional scarring and vision loss.[104]

Management of Complications

• Regular monitoring and early intervention: Early detection and management of complications are crucial. Regular follow-up visits and advanced imaging techniques can help monitor the progression and detect complications early.
• Customized treatment plans: Treatment plans should be tailored to the individual patient's needs, considering the severity of the disease and any associated complications. Measures may include the use of customized contact lenses, CXL, or surgical interventions.
• Psychological support: Providing psychological support and counseling can help patients cope with the emotional impact of the disease and improve their overall well-being.

Understanding and managing the complications associated with superior keratoconus can help healthcare providers improve patient outcomes and quality of life.