Keratopathy

Etiology

Band shaped keratopathy (BSK): Chronic ocular inflammation like uveitis, chronic herpetic keratouveitis; phthisis bulbi, keratoconjunctivitis sicca, juvenile idiopathic arthritis, and long-standing silicone oil in the eye may lead to calcific band-shaped keratopathy.[1] BSK may be associated with systemic disorders including hyperparathyroidism, vitamin D toxicity, sarcoidosis, nephropathic cystinosis, hypophosphatemia, Paget's disease, multiple myeloma, and familial band-shaped keratopathy.[2][3]

Pseudophakic bullous keratopathy (PBK) and aphakic bullous keratopathy (ABK): PBK manifests largely due to damage caused to the endothelial cells. The endothelial cells are responsible for maintaining the relatively dehydrated state of the cornea. Irreversible damage to endothelial cells manifests in corneal edema. The intraoperative damage caused to endothelium by instrumentation, ultrasonic energy during phaco, and exposing endothelium to toxic solutions leads to endothelial damage.[4] Intense inflammation, toxic anterior segment syndrome, and raised intraocular pressure also add to the damage post-operatively.[5]

In ABK, vitreous is the major insulting agent causing damage to the endothelium due to vitreo-corneal touch.[6] This results in the death of endothelial cells and subsequent ABK. 

Striate keratopathy: Striate keratopathy is characterized by the presence of corneal edema with Descemet's folds after cataract surgery in an eye with a relatively healthy and clear cornea and in the absence of obvious Descemet's membrane detachment.[7] The edema is maximum on day 1 and improves as the day passes off. Hypertonic saline in conjunction with topical steroids, helps edema clear off completely over weeks.[8]

Corneas with pre-existing compromised but non-decompensated endothelial pumps are largely at risk of developing striate keratopathy.[9] However, the use of excessive ultrasonic energy during phacoemulsification can cause this condition even in the cornea with absolutely normal endothelium. If a toxic substance permeates into the anterior chamber through the surgical incision during surgery, it can cause severe grades of inflammation (toxic anterior segment syndrome).[10]

Whorl (vortex) keratopathy or cornea verticillata: Agents causing whorl keratopathy include amiodarone, chloroquine, hydroxychloroquine, phenothiazines, tamoxifen, indomethacin, and many other pharmacologic agents.[11][12][13] Non-pharmacological conditions associated with whorl keratopathy include Fabry's disease, multiple myeloma, Lisch corneal dystrophy, post- radial keratotomy, and other diseases.[14][15]

Exposure keratopathy: Exposure keratopathy is a consequence of the inability to maintain uniform tear film distribution over the ocular surface. Tear film helps in maintaining the epithelial integrity and thus prevents any epithelial denudation. Decreased corneal sensation, decreased blink reflex, decreased blink rate, proptosis, lagophthalmos (paralytic, cicatricial, nocturnal), poor Bell's phenomenon, and severe lid deformities (lid coloboma, cicatricial ectropion, post-excision of lid tumor) causing exposure may result in abnormal tear film distribution over the ocular surface. 

Infectious crystalline keratopathy (ICK): It is a rare gray-white branching corneal opacity in the corneal stroma with minimal to absent surrounding inflammation. This is seen in cases associated with prolonged topical steroid use. This is seen mostly in cases with previous penetrating keratoplasty. The most common inciting organism is alpha-hemolytic Streptococcus viridians. Other organisms reported include S. Pneumoniae, coagulase-negative Staphylococcus, Peptostreptococcus, Haemophilus species, Mycobacterium species, Pseudomonas, Candida species, and many more.[16][17][18][19]

Neurotrophic keratopathy: Neurotrophic keratopathy may occur post-herpes zoster ophthalmicus (post-HZO) and after trigeminal nerve damage due to surgery or tumor.[20]

Metabolic Keratopathy: Metabolic keratopathy manifests due to enzymatic defect along the normal metabolic pathway. The toxic byproducts accumulate in the different parts of the body including the cornea.

• Mucopolysaccharidoses: Here enzymes necessary to degrade different mucopolysaccharides are deficient resulting in their accumulation. 
• Cystinosis: Mutation of cystinosin results in the accumulation of cystine crystals in the cornea.
• Wilson's disease: Deficiency of Wilson disease protein (ATP7B) results in the accumulation of copper in different parts of the body including the cornea. 
• Lecithin-Cholesterol Acyltransferase (LCAT) deficiency: Lecithin-cholesterol acyltransferase deficiency results in increased unesterified cholesterol, triglycerides, and phospholipids and manifests as corneal arcus, corneal stromal haze, and angioid streaks.

Filamentary keratopathy: It is a chronic disorder in which, filaments made of mucus and epithelial debris are attached at one end to the corneal surface. The various causes are:

• Keratoconjunctivitis sicca,
• superior limbic keratoconjunctivitis,
• exposure keratitis,
• corneal edema,
• neurotrophic keratopathy,
• Sjogren's syndrome,
• chronic use of anticholinergic medication, and many other conditions.

Climatic droplet keratopathy/Labrador keratopathy/Spheroidal degeneration: This results from the photochemical degradation of plasma proteins by UV light.

Lipid keratopathy: This is a degenerative condition of the cornea, where lipid degeneration occurs. Disorders of lipid metabolism and Herpetic corneal infection are the major causes of lipid keratopathy. The vascularization brings the lipid into the corneal stroma.

Superficial punctate keratopathy (SPK): It is a non-specific clinical finding of varied etiology characterized by the punctate loss of epithelial cells. The various causes are viral keratoconjunctivitis, keratoconjunctivitis sicca, blepharitis, chemical injury, contact lens wear, toxic keratopathy due to topical medications, Bell's palsy, ultraviolet ray exposure, and many other causes.

Ultraviolet (UV) keratopathy: The corneal burn caused by UV-B results in UV keratopathy. Causes include welding arc exposure and light reflected from the snow.

Toxic keratopathy- Dendritiform keratopathy may be noted due to polyquaternium-1 (preservative).

Keratopathy related to vernal keratoconjunctivitis (VKC): The keratopathy is largely due to the mechanical effect of papillae and also due to the release of various cytokines.

Keratopathy related to Stevens-Johnson syndrome (SJS)/ toxic epidermal necrolysis (TEN): Most of the cases of SJS or TEN are related to hypersensitivity reactions to a medication or its metabolite. In some cases, viral fever can also act as a trigger.[21] Sulphonamides, analgesics, anti-epileptics, and many other drugs may act as offending agents.

Keratopathy associated with aniridia: Keratopathy associated with aniridia is poorly understood and the changes are likely secondary to limbal stem cell deficiency (LSCD).

Epidemiology

In a study on the risk of band-shaped keratopathy in patients with end-stage renal disease, the incidence was found to be around 0.14%.[22] Bullous keratopathies may occur in 1% to 2% of patients undergoing cataract surgery worldwide and this equals almost 2 to 4 million patients worldwide.[23] 

In a study by Bates et al, out of 30 cases of keratitis following penetrating keratoplasty, they found 5 cases of infectious crystalline keratopathy.[24] In SJS and TEN, 43-89% of cases develop chronic ocular complications, of which, Keratopathy is an important component.[25][26][27][28] In a study, keratopathy was found to be present in 89% of aniridic eyes.[29]

Pathophysiology

Band shaped keratopathy: There is an imbalance in the calcium and phosphate metabolism resulting in deposition of calcium phosphate crystals into the subepithelial Bowmans layer, epithelial basement membrane, and anterior stroma. The various local and systemic causes have been mentioned in the etiology section. There exists a lucent gap between the limbus and the BSK. This peripheral clearing is likely due to the absence of Bowmans's membrane in the periphery or buffering capacity of limbal vessels that prevents the deposition of hydroxyapatite. Holes in the BSK gives it a swiss cheese appearance and is because of corneal nerves traversing the Bowman's membrane.

Pseudophakic and aphakic bullous keratopathy: The endothelium is largely responsible for the maintenance of a relatively dehydrated state of cornea apart from tight junctions of the epithelium. Damage caused by ultrasonic energy during phacoemulsification apart from iatrogenic damage during instrumentation results in endothelial cell loss. The surrounding endothelial cells slide horizontally to fill in the gaps caused by endothelial cell death.[30][31] Literature suggests the non-replicative property of endothelium.[32] So, the workload of remaining endothelial cells to keep cornea dehydrated increases by manifolds.[33] When the remaining endothelial cells also get compromised, then the ABK or PBK manifests. 

Striate keratopathy: Transient endothelial dysfunction due to intra-operative insult to endothelium results in striate keratopathy. 

Whorl keratopathy: The various medications owing to the amphiphilic nature reaches the lipids of lysosomal membranes of the basal epithelial layer. There they form an insoluble complex with lipids and appear as deposits.[11] However, in Fabry's disease, the deficiency of alpha-galactosidase-A results in the accumulation of glycosphingolipid products in lysosomes of the entire body including the cornea.[15]

Exposure keratopathy: Tear film is an important part of the defense mechanism and also has its role in the nourishment of cornea. Its maintenance is of utmost importance. A normal corneal sensation, a normal blink rate, healthy lid anatomy, and appropriate innervation are required for its maintenance. If any of these get altered, the tear film will also get affected. Absent tear film from a part of the ocular surface will make the surface dry and more prone to epithelial denudation and infection.

Infectious crystalline keratopathy (ICK): ICK is largely caused by biofilm-producing organisms. The presence of biofilms protects the bacteria in a well sequestered intrastromal pocket. There is minimal or no inflammation in the surrounding area. The organisms usually enter the corneal stroma along suture tracks. 

Neurotrophic keratopathy: Damage to the trigeminal nerve nuclei, or the trigeminal nerve fascicle in its course results in the neurotropic cornea. HZO is a major cause.

Metabolic keratopathy: 

Mucopolysaccharidoses (MPS): There are various types of MPS, depending on the type of enzyme deficiency. In MPS I (Hurler's syndrome), deficiency of alpha iduronidase results in the accumulation of heparan and dermatan sulfate. In MPS II (Hunter's syndrome), there is a deficiency of iduronate -2-sulfatase. Corneal clouding is noted in almost all types of MPS except type II and III. It is never noted in MPS III but maybe rarely observed in MPS II.

Cystinosis: Here, deficiency of cystinosin results in the accumulation of cystine in the cornea. The corneal manifestations (needle-like crystal deposition) manifest very early in life. 

Wilson's disease: This abnormality of copper metabolism results in the accumulation of copper in the cornea, putamen, and liver. In the cornea, copper deposits largely in the Descemet's membrane forming a ring called Kayser-Fleischer (KF) ring. 

Lecithin-Cholesterol Acyltransferase deficiency results in decreased cholesterol esters and lysolecithin and increased unesterified cholesterol, triglycerides, and phospholipids. The deposition of these unesterified forms results in the deposition in the corneal layers in the peripheral cornea.

Filamentary keratopathy: In aqueous deficient dry eyes, lack of tear production results in excessive production of mucus by goblet cells. The epithelial injury along with the mucus debris results in filament formation. 

Climatic droplet keratopathy: This is a degeneration of cornea and/or conjunctiva characterized by diffusion and coagulation of plasma proteins into the superficial corneal stroma, bowman's membrane, and epithelium, in response to exposure to UV radiation. It is also known as spheroidal degeneration and Labrador keratopathy. 

Lipid keratopathy:  There is abnormal lipid deposition and /or metabolism of lipid in the cornea.

Superficial punctate keratopathy: Punctate epithelial loss results in punctate staining with fluorescein stain.

Keratopathy related to vernal keratoconjunctivitis: It is IgE mediated and TH2 cell-mediated reaction.[34][35]

Keratopathy related to SJS/TEN: In patients with SJS, there are changes in ocular surface changes secondary to epithelial denudation. In the chronic phase, severe dry eye and the lid margin changes like keratinization, scarring of the tarsal conjunctiva cause blink related trauma to the ocular surface including the cornea. This results in keratopathy.[36]

Keratopathy related to aniridia: The total LSCD results in epithelial changes followed by complete conjunctivalization of the cornea.

History and Physical

Band shaped keratopathy: The patient might give a history of chronic uveitis, vitreoretinal surgery with silicone oil in-situ, or a history of some systemic disease known to cause band-shaped keratopathy. Patients with juvenile idiopathic arthritis may give a history of multiple joint pain. History of trauma or long-standing recurrent uveitis can be elicited in patients with a band-shaped keratopathy associated with phthisis bulbi. The patient usually presents with complaints of decreased visual acuity, foreign body sensation, and poor cosmesis. On clinical examination, there is a band-shaped, greyish white, plaque-like lesion extending from the periphery towards the central cornea in the inter-palpebral region. However, there is a lucent zone separating the BSK from the limbus. There are multiple holes in the BSK through which corneal nerves traverse, giving it swiss-cheese appearance.

PBK and ABK: A history of complicated cataract surgery with or without anterior chamber intraocular lens (ACIOL) is often elicited. The patient gives a history of delayed visual recovery after cataract surgery. Though, an interval with relatively good vision after cataract surgery and before the onset of PBK and ABK can also be elicited. On examination, diffuse corneal stromal edema with the presence of epithelial bullae and Descemet's folds will be evident. In long-standing cases of PBK and ABK, subepithelial scarring develops. The epithelium hypertrophies and vascularization occurs. The thick opaque pannus over the cornea may prevent anterior chamber visualization. 

Striate keratopathy: It is characterized by the presence of corneal stromal edema and Descemet's folds. Usually, the radiating Descemet's membrane folds are located close to the incision or more centrally. The corneal clarity decreases significantly and is proportional to the degree of intraoperative insult caused. A history of prolonged surgery or complicated surgery can be elicited. 

Whorl keratopathy: Golden brown opacities at the level of basal epithelial cells arranged in a whorl can be seen on slit-lamp examination. The whorls start from the center and branch in the periphery. The lesions are noted bilaterally. A history of the use of causative medications can be elicited.[15]

Exposure keratopathy (EK): In cases with exposure keratopathy secondary to nerve damage, the history of parotid surgery/ tumor can be elicited in some. In some cases, the clinician gets a call from intensive care units (ICU) for patients who are bedridden for an extended period. In cases with EK secondary to lid abnormality, obvious coloboma (congenital or acquired) or ectropion can be seen. Proptosis can also be noted. Corneal epithelial defect and underlying stromal edema involving the lower half of the cornea can be noted. Secondary infection with microbial agents results in the infiltration of inflammatory cells into the cornea. 

Infectious crystalline keratopathy: The history of previous penetrating keratoplasty and prolonged use of topical steroids is likely to be present in most of the cases. The patient presents with mild discomfort, years after penetrating keratoplasty. The patient presents with grayish-white needle-like branching corneal stromal lesion with decreased vision and minimal to no inflammation surrounding the opacity.[37]

Neurotrophic keratopathy: Corneal sensations decrease significantly after HZO, resulting in recurrent corneal erosions in the chronic phase. The epitheliopathy may result in persistent epithelial defects and subsequent stromal ulceration. The ulcer is called 'neurotrophic ulcer.'[38]

Metabolic keratopathy: All metabolic keratopathies are bilateral and present since early in life. MPS presents with diffuse corneal haze due to the diffuse deposition of mucopolysaccharides in the cornea. In cystinosis, needle-like crystal deposits are noted in the anterior peripheral stroma. Recurrent corneal erosion is commonly associated with it. Blepharospasm and photophobia are common. It is associated with grossly altered renal functions. In LCAT deficiency, arcus at a younger age is noted. Corneal stromal haze and retinal angioid streaks are also noted. 

Filamentary keratopathy: The patient typically presents with foreign body sensation, blurring of vision, excessive tearing, frequent blinking, photophobia, and blepharospasm. On examination, corneal filaments are noted along with redness. 

Climatic droplet keratopathy: This is a type of corneal degeneration, where golden yellow spherules of varying sizes get deposited in the anterior stroma, bowman's membrane, and epithelium. The patient usually gives a history of prolonged exposure to sunlight. This causes a foreign body sensation and lacrimation if elevated. If the central cornea is involved then visual acuity also declines.

Lipid keratopathy: The patient gives a history of gradual decline in visual acuity. The patient might give a history of recurrent episodes of redness associated with viral keratitis. On examination, lipoidal infiltration into the cornea can be seen as a whitish lesion often arising in close vicinity of a vessel. 

Superficial punctate keratopathy and vernal keratoconjunctivitis related keratopathy: On examination, punctate fluorescein stating is noted. In patients with giant papillae, the SPKs are largely located in the superior half of the cornea; whereas, in patients with keratoconjunctivitis sicca there exists diffuse SPK. Patients might give a history of contact lens wear. The patient presents with pain, photophobia, and redness.

However, in VKC related keratopathy, shield ulcer, pseudogerontoxon, and limbal thickening can also be noted. Horner-Trantas dots are characteristically present over the limbus.

Ultraviolet keratopathy: The disease manifests as superficial punctate keratopathy. A history of either seeing a welding arc or trekking in snowcapped terrain may be elicited. 

Keratopathy related to SJS/TEN: On examination, one can notice keratinization of lid margins, tarsal conjunctival scarring, and posterior migration of mucocutaneous junction in late stages. All these changes together are responsible for recurrent microtrauma to the cornea. Total limbal stem cell deficiency manifests as vascularization and conjunctivalization or dermalization of the cornea. 

Keratopathy related to aniridia: The epithelium is abnormal and results in the thickening of the epithelium over time. Peripheral pannus develops, which progresses centrally ultimately causing complete conjunctivalization.

Evaluation

Band shaped keratopathy: The diagnosis of band-shaped keratopathy is largely clinical. The slit-lamp examination reveals the typical appearance and its subepithelial location. The exact cause of the lesion needs to be ascertained. To rule out systemic causes of band-shaped keratopathy, various serological tests are performed which include serum calcium, serum parathormone, serum phosphate/phosphorus, serum ACE (angiotensin-converting enzyme), serum vitamin-D levels, urine analysis, chest X-ray, and other tests.

PBK and ABK: The diagnosis is made based on clinical evaluation. A history of complicated cataract surgery or delayed visual recovery is almost always elicited. Owing to the presence of thick opaque pannus over the cornea, visualization of anterior chamber structures may not be feasible. Anterior segment optical coherence tomography (ASOCT) is an important tool to assess the corneal thickness, the extent of subepithelial scarring, and the gross abnormality of Descemet's membrane. Specular count of the endothelial cells and their morphology in the fellow eye is needed.

Striate keratopathy: The slit-lamp examination helps differentiate between corneal edema secondary to Descemet's membrane detachment (DMD). ASOCT may be performed to confirm the absence of DMD.

Whorl keratopathy: Slit-lamp examination reveals bilateral golden brown deposits in the basal epithelial layer of the cornea. If no chronic systemic medication is found, systemic investigations to rule out systemic associations should be done which include α-galactosidase activity.

Exposure keratopathy: The diagnosis is largely clinical. The inferior location of corneal ulceration is very typical. The exact cause should be looked for. The tone of orbicularis oculi muscle is assessed. Status of Bell's phenomenon, lid lag, or lid abnormalities is looked for. Cicatricial ectropion, Bell's palsy, and proptosis may be self-evident.  

Infectious crystalline keratopathy: Clinical examination along with corroborative history, helps clinicians make a diagnosis of ICK. A tissue biopsy can yield the causative organism.

Neurotrophic keratopathy: The diagnosis of neurotrophic keratopathy is based on history and clinical findings. 

Metabolic keratopathy: In all metabolic keratopathy, bilaterality in association with systemic features suggest the disease. In MPS, the systemic features and corneal findings are very suggestive; however, the diagnosis of a specific type of MPS needs assay of deficient enzyme/s. For diagnosing cystinosis, the leucocyte cystine level and conjunctival biopsy are done to measure the free cystine level. Renal functions are also grossly altered. Anterior segment optical coherence tomography can be used to assess the depth of involvement. For Wilson's disease, 24-hours urine collection shows elevated levels of urine copper. Serum ceruloplasmin levels are decreased in the majority of cases of Wilson's disease. 

Filamentary keratopathy: The diagnosis is made based on the clinical findings. The systemic causes of aqueous deficient dry eye are looked for, using a battery of serological tests. 

Climatic droplet keratopathy and Lipid keratopathy: The diagnosis is based on clinical examination.

Superficial punctate keratopathy (SPK) and ultraviolet keratopathy: The patients when examined on a slit-lamp after staining with fluorescein stain under cobalt blue filter shows areas of punctate corneal staining. The distribution of SPKs suggests the etiology. 

Keratopathy related to SJS/TEN: Schirmer's test shows severe aqueous deficient dry eye. On slit-lamp examination, using fluorescein dye posterior migration of mucocutaneous junction can be demonstrated. Other features like lid margin keratinization, dermalization, and pannus over cornea can be seen on a slit-lamp.

Keratopathy related to aniridia: The diagnosis is largely clinical.

Treatment / Management

Band-shaped keratopathy: Surgical removal of band-shaped keratopathy is the main treatment modality; however, the local and systemic cause of band-shaped keratopathy needs to be controlled before surgical correction. Epithelial debridement followed by chelation with EDTA (ethylenediaminetetraacetic acid) is the main treatment modality.[39] Recurrence is common if the primary disease is not controlled. In cases with BSK, with no vision potential, patients should be counseled for colored contact lens also. Superficial lamellar keratectomy, EDTA chelation coupled with amniotic membrane transplantation has also been described.[40](B2)

PBK and ABK: PBK and ABK are the end result of endothelial cell loss during cataract surgery. The only treatment is replacing the damaged endothelial cells with healthy endothelial cells from a donor cornea. Descemet's stripping endothelial keratoplasty (DSEK) and Descemet's membrane endothelial keratoplasty (DMEK) is the viable treatment options.[41] Penetrating keratoplasty may be needed in cases with corneal stromal scarring. For cases with no vision potential (cases with compromised optic nerve head), anterior stromal puncture with or without Amniotic membrane transplantation is an option. This procedure induces subepithelial scarring and prevents bullae formation. Thus the patients are relieved of the symptoms caused by recurrent rupture of bullae. 

Striate keratopathy: Topical steroids is the mainstay of treatment. Depending on the degree of striate keratopathy the dose of topical steroids have to be tailored. Hypertonic saline drops or ointments may be added according to the severity.

Whorl keratopathy: The deposits in whorl keratopathy are not visually significant and thus need not be treated. On discontinuing the causative medication this resolves. However, reports of using topical heparin for whorl keratopathy are available.[42]

Exposure keratopathy: Instillation of frequent artificial tears, lubricating gel, and nighttime taping is an option in Bell's palsy associated exposure keratopathy. The same treatment regimen is also advised prophylactically for patients admitted in Intensive Care Units. Topical prophylactic antibiotics are also added to the regimen to avoid secondary bacterial infection. Lateral paramedian or central tarsorrhaphy is done depending on the degree of lagophthalmos and status of Bell's phenomenon.[43]

In Exposure keratitis secondary to proptosis, the actual cause of proptosis needs to be addressed. In Thyroid eye disease (TED), systemic control is of utmost importance and is also combined with orbital decompression surgeries in severe cases. If the proptosis is secondary to some orbital tumor then, that needs to be taken care of simultaneously.

For exposure keratopathy secondary to congenital or acquired lid coloboma, a pedicle graft or flap needs to be done. 

Infectious crystalline keratopathy: In view of resistance to medical management, the definitive management will be re-doing of the penetrating corneal graft. Medications can be tailored based on the biopsy report (culture, sensitivity, and histopathology).[44](B3)

Neurotrophic keratopathy: Neurotrophic ulcers are managed with serum, amniotic membrane transplantation, and tarsorrhaphy. FDA (Food and drug administration, USA) has approved cenegermin-bkbj ophthalmic solution (1 drop to be used 6 times a day for 8 weeks) for this indication.

Metabolic keratopathy: Corneal stromal haze in MPS often requires a lamellar or full-thickness corneal transplant. KF ring per se is not visually significant and does not require treatment. Treatment of Wilson's disease though has to be given. Topical cysteamine drops (0.55%) can help dissolve cystine crystals; however, the severe cases often require penetrating keratoplasty. There is always a risk of recurrence in the graft also. Systemic cysteamine may help to decrease the severity of the disease.

Filamentary keratopathy: Treatment of the underlying dry eye is of utmost importance. Proposed treatments include topical lubricants (drops and ointment) and topical steroid/nonsteroidal agents.[45] Mechanical removal of filaments, the use of hypertonic saline, mucolytic agents, the use of punctal plugs, and bandage contact lens have also been advocated.[45] The systemic disease like underlying connective tissue disease has to be controlled simultaneously to avoid recurrence.(B3)

Climatic droplet keratopathy: Treatment needs to be tailored for individuals depending on the location, extent, and severity. If visual acuity is getting hampered, then one can plan for superficial keratectomy with amniotic membrane transplantation, phototherapeutic keratectomy, lamellar keratoplasty, and penetrating keratoplasty, depending on the severity.[46][47][48](B3)

Lipid keratopathy: The vessels bringing lipoidal infiltrates into the cornea are cauterized. Subconjunctival and intracorneal anti-VEGF (vascular endothelial growth factor) therapy has also been given to prevent further infiltration of lipids.[49] Penetrating keratoplasty is a known modality to restore vision. Cogan's syndrome needs to be ruled out in cases with associated deafness. (B3)

Superficial punctate keratopathy and ultraviolet keratopathy: Lubricants are the mainstay in SPKs. However, one should also take care of the offending agents, like contact lenses and giant papillae. Contact lens should be discontinued and giant papillae should be treated with intralesional steroids in addition to topical lubricants.

VKC related keratopathy: Treatment of ocular allergy with topical steroids, mast cell stabilizers, and antihistaminics helps in keratopathy also. Lubricants are also added to the treatment regimen. Topical tacrolimus or cyclosporine are being used as steroid-sparing agents.[50] Oral antihistaminics also have a proven role.(B2)

Keratopathy related to SJS/TEN: The Mucous membrane graft (MMG) works well in children over PROSE (prosthetic replacement of ocular surface ecosystem) lens; whilst, PROSE  works better than MMG in adults. PROSE and MMG when combined together, give superior outcomes in both adults and children.[51](B3)

Keratopathy related to aniridia: Limbal stem cell transplantation followed by penetrating keratoplasty is the treatment option available.

Differential Diagnosis

Band shaped keratopathy: Spheroidal degeneration and Salzmann nodular degeneration are important differentials of BSK.

PBK and ABK: Corneal decompensation secondary to Fuchs' endothelial dystrophy is an important differential. Examination of the other eye helps differentiate between two. 

Striate keratopathy: Corneal edema secondary to Descemet's membrane detachment is an important differential.

Whorl keratopathy: Iron lines are among the major differentials.

Exposure keratopathy: Inferiorly located corneal ulcer is an important differential diagnosis.

Infectious crystalline keratopathy: Bacterial keratitis, viral keratitis, fungal keratitis, cystinosis, Bietti crystalline dystrophy, Schnyder crystalline dystrophy, and many other conditions mimic ICK.

Metabolic keratopathy: Being bilateral and diffuse in cases of MPS, it may get confused with corneal dystrophies like congenital hereditary endothelial dystrophy or congenital hereditary stromal dystrophy. Arcus can be a differential diagnosis for the KF ring.

Filamentary keratopathy: One differential is mucus debris on the ocular surface. 

Climatic droplet keratopathy: The fine variants of spheroidal degeneration are often mistaken for microcystic corneal edema.

Lipid keratopathy: Interstitial keratitis is an important differential.

Superficial punctate keratopathy: Microsporidial keratoconjunctivitis and Thygeson's punctate keratopathy are major differential diagnoses for SPK.

VKC related keratopathy: Atopic keratoconjunctivitis is the major differential.

Keratopathy related to SJS/TEN: Mycoplasma induced rash and mucositis; and erythema multiforme are major differential diagnoses.

Prognosis

Band shaped keratopathy: BSK is a degenerative process that usually develops in chronically inflamed eyes. BSK per se causes visual impairment and cosmetic blemish.

Pseudophakic and aphakic bullous keratopathy: These are the end results of corneal decompensation. Endothelial keratoplasty is an option to treat the condition. However, if it persists for longer, it induces anterior stromal scarring and pannus development over the cornea. 

Striate keratopathy: Usually, striate keratopathy clears up completely over 3 to 4 weeks with topical steroid.

Whorl keratopathy: It is not visually significant. It vanishes once the medication causing it is stopped.

Exposure keratopathy: If left untreated, the epithelial defect progresses and later corneal stromal melting ensues. In long-standing cases, corneal perforation develops. Secondary bacterial infection is very common.

Infectious crystalline keratopathy: ICK is resistant to medical therapy and often needs therapeutic penetrating keratoplasty as a rescue.

Metabolic keratopathy: In the absence of treatment, the MPS may result in complete opacification of the cornea. The systemic features and manifestations may be severe enough in some MPS to cause death. Similarly, the KF ring in Wilson's disease does not cause any visual obscuration; however, the systemic manifestations of Wilson's disease may be fatal.

Filamentary keratopathy: Usually gets controlled with the above-discussed management strategies. For recurrent cases, the systemic cause needs to be thoroughly looked for and controlled.

Climatic droplet keratopathy: This progresses with continued exposure to sunlight.

Superficial punctate keratopathy: This often resolves once the offending agents (like contact lenses, giant papillae) are taken care of. 

Keratopathy related to SJS/TEN: The end-stage is a severe dry with limbal stem cell deficiency with a completely dermalized ocular surface.

Complications

Band shaped keratopathy: Visual impairment and cosmetic blemish are the major concerns.

Pseudophakic and aphakic bullous keratopathy: A vascularized thick pannus grows over edematous corneal stroma with complete loss of corneal transparency. The development of infectious keratitis is a major concern.

Striate keratopathy: Delayed recovery or no recovery is a concern, depending on the degree of damage to the endothelium. 

Whorl keratopathy: This does not per se cause any complication; however, it might be an indicator of systemic disease, like Fabry's disease.

Exposure keratopathy: Corneal ulcer formation and auto-evisceration are major concerns here.

Infectious crystalline keratopathy: A flare-up of indolent infection may occur. 

Metabolic keratopathy: If left untreated complete corneal haze is likely to develop in cases of MPS.

Filamentary keratopathy: The risk of development of microbial keratitis is higher, especially if the bandage contact lens is used.

Climatic droplet keratopathy: There is a risk of development of microbial keratitis.

VKC related keratopathy: Shield ulcer, keratoconus are the known complications.

Keratopathy related to SJS/TEN: Complications include microbial keratitis and corneal melt.