Keratoconus - A Complete Overview

Definition

Epidemiology

• Prevalence: ~0.1-0.2% (approximately 55 cases per 100,000 in the US), though subclinical cases likely make this an underestimate
• Age of onset: Typically during the teens or twenties; rarely congenital
• Sex: Men are slightly more affected than women
• Laterality: Almost always bilateral, but commonly asymmetric at presentation. About 50% of normal fellow eyes will progress to KC within 16 years; virtually all cases become bilaterally affected on topographic imaging eventually

Etiology & Pathogenesis

• Most patients have no family history; only ~10% of offspring develop KC
• Autosomal dominant transmission with incomplete penetrance has been proposed
• Associated with chromosomal loci on several chromosomes (VSX1, SOD1, and others)

• Degradation of stromal collagen fibrils and loss of lamellar organization
• Increased activity of proteolytic enzymes (matrix metalloproteinases) causes collagen breakdown
• Oxidative stress and free radical damage to stromal keratocytes play a role
• Result: focal stromal thinning, cornea loses its structural integrity and bulges forward under intraocular pressure

• Chronic eye rubbing is a well-established risk factor and driver of progression - rubbing likely induces cytokine release (IL-1, TNF-alpha) causing keratocyte apoptosis

Risk Factors & Associations

• Down syndrome (trisomy 21) - most common
• Ehlers-Danlos syndrome
• Marfan syndrome
• Osteogenesis imperfecta
• Turner syndrome
• Sleep apnea / floppy eyelid syndrome
• Mitral valve prolapse
• Leber congenital amaurosis
• Retinitis pigmentosa

• Vernal keratoconjunctivitis (atopic disease)
• Allergy, asthma, eczema (the chronic rubbing from these drives KC)
• Blue sclera
• Aniridia

• Chronic eye rubbing (from any cause)

Grading (by keratometry)

Clinical Features

Symptoms

• Progressive decrease in vision - progressive myopia and irregular astigmatism
• Monocular diplopia, ghosting of images
• Starbursts and halos around lights
• Frequent changes in spectacle prescription
• In acute hydrops: sudden painful decrease in vision, red eye, photophobia, profuse tearing

Signs - Examination Findings

Fig. A: Classic "oil droplet" red reflex on direct ophthalmoscopy (Kanski's Clinical Ophthalmology)

• Irregular "scissoring" or "water droplet" reflex due to irregular astigmatism

Fig. C: Fleischer ring demonstrated with cobalt blue light (arrow) (Kanski's Clinical Ophthalmology)

Fig. D: Typical cone-shaped corneal protrusion (Kanski's Clinical Ophthalmology)

• Steep irregular readings; egg-shaped ("mire") distortion

• Inferior steepening is characteristic
• Topographic progression: symmetrical bow-tie pattern → asymmetrical → inferotemporally displaced steep-sided cone (sometimes a central "nipple" cone)
• Tomography (Pentacam/Scheimpflug imaging) shows posterior corneal elevation, anterior thinning, and inferior displacement of the thinnest corneal point

Acute Corneal Hydrops

• Mechanism: Stretching and rupture of Descemet membrane allows aqueous humor to suddenly flood the corneal stroma
• Symptoms: Acute severe decrease in vision, pain, red eye, photophobia, profuse tearing
• Course: Descemet membrane usually heals within 6-10 weeks; edema clears, but variable stromal scarring may develop (which can paradoxically flatten the cone and sometimes improve vision)

• Cycloplegic agent (e.g., cyclopentolate 1% TID) for pain relief if anterior chamber reaction present
• Aqueous suppressant (e.g., brimonidine 0.1% BID-TID)
• Sodium chloride 5% ointment BID-QID until resolved (typically weeks to months)
• Consider topical steroids to suppress corneal neovascularization
• Protective eyewear (shield)
• Intracameral gas (air, SF6, or C3F8) may speed resolution but carries risks (cataract, pupillary block glaucoma)
• Note: Acute hydrops is NOT an indication for emergency corneal transplantation

Workup & Diagnosis

1. History: Rate of visual decline, frequency of prescription changes, eye rubbing, allergies, family history, previous refractive surgery
2. Slit-lamp exam: Vogt striae, Fleischer ring, thinning, scarring
3. Retinoscopy and refraction: Irregular astigmatism, scissors reflex
4. Corneal topography: Shows central/inferior steepening
5. Corneal tomography (Pentacam/Scheimpflug): Gold standard - shows posterior elevation, thinning map, and pachymetry; detects subclinical ("forme fruste") keratoconus
6. Keratometry: Irregular mires and steep values

Differential Diagnosis

Treatment

Step 1 - Stop Eye Rubbing

Step 2 - Optical Correction

Step 3 - Corneal Collagen Cross-Linking (CXL)

• Mechanism: Riboflavin (vitamin B2) photosensitizer is applied to the cornea, then ultraviolet-A (UVA) light is applied - this creates new covalent bonds between collagen fibrils, stiffening the cornea
• Standard (epi-off) protocol: 9 mm epithelial debridement → riboflavin drops for 30 min → UVA exposure for 30 min
• Epi-on (transepithelial): Less effective in older evidence, though recent meta-analyses (PMID: 40856685) continue comparing these approaches
• Efficacy: >90% success in halting progression; can sometimes reverse ectasia
• FDA approval: Ages 14 and older (off-label for younger children)
• Complication: Small risk of infection or corneal scarring (bandage contact lens used for ~3 days post-procedure; 1-2 weeks for stabilization)
• Indication: Documented progressive disease

Step 4 - Intracorneal Ring Segments (ICRS)

• Polymethylmethacrylate (PMMA) segments inserted into the corneal stroma via laser or mechanical channels (e.g., Intacs, Ferrara rings)
• Mechanically flattens the cone, reduces irregular astigmatism
• Facilitates contact lens tolerance in moderate-advanced cases
• Can be combined with CXL
• Does NOT halt progression on its own

Step 5 - Corneal Transplantation

• Outcomes may be compromised by residual astigmatism and anisometropia, often requiring contact lens correction even after transplant
• LASIK is absolutely contraindicated in keratoconus patients; pre-operative screening for KC is mandatory before any corneal refractive surgery

Prognosis

• Progression typically occurs over 5-10 years, then may stabilize
• Most patients with mild-moderate disease maintain functional vision with contact lenses
• Corneal transplant success rates are high (~90%), but residual optical correction is often still needed
• Quality of life is significantly impacted, particularly in advanced disease (PMID: 40877860)

Key Points Summary

1. KC is a progressive non-inflammatory corneal ectasia - thinning + cone-shaped protrusion + irregular astigmatism
2. Prevalence ~0.1-0.2%; bilateral but asymmetric; onset in teens/twenties
3. Hallmark slit-lamp signs: Vogt striae, Fleischer ring, Munson sign, oil-droplet reflex
4. Diagnosis confirmed with corneal topography/tomography (Pentacam)
5. Stop eye rubbing is the most important behavioral intervention
6. CXL halts progression and is first-line for progressive disease
7. Contacts (RGP/scleral) are the backbone of vision rehabilitation
8. Severe disease unresponsive to lenses → DALK or PK
9. LASIK is absolutely contraindicated
10. Acute hydrops = Descemet rupture → managed conservatively, not with emergency transplant

Recent evidence note: A 2025 meta-analysis (PMID: 40856685) continues to compare epi-on vs. epi-off CXL - overall, epi-off remains more effective for halting progression. Deep learning tools are also emerging for earlier KC detection (PMID: 38300179).