CONGENITAL CLOUDY CORNEA

A variety of genetic, metabolic, developmental, and idiopathic causes can result in congenital clouding of the cornea. Note the image below.

Clouding of the cornea since childhood.

A common reason for congenital clouding of the cornea is congenital glaucoma.

Other major causes of corneal clouding include the following:

• Birth trauma
• Peters anomaly
• Dermoid tumors (limbal dermoids)
• Sclerocornea
• Congenital hereditary endothelial dystrophy (CHED)
• Mucopolysaccharidoses
• Infectious/inflammatory processes

The following is a mnemonic for the causes of congenital clouding of the cornea:

• S - Sclerocornea
• T - Tears in the Descemet membrane secondary to birth trauma or congenital glaucoma
• U - Ulcers
• M - Metabolic
• P - Peters anomaly
• E - Edema (CHED)
• D – Dermoid

Other rarer causes of congenital clouding of the cornea include the following: cornea plana, corneal keloids, oculoauriculovertebral (OAV) dysplasia (Goldenhar-Gorlin syndrome), congenital corneal ectasia, congenital hereditary stromal dystrophy, posterior polymorphous dystrophy, and Fryns syndrome.

Sclerocornea

Sclerocornea is an uncommon developmental abnormality of the anterior segment due to mesenchymal dysgenesis. Sclerocornea manifests as a stationary congenital anomaly. It is usually seen as an isolated ocular abnormality involving both eyes, although it can occur unilaterally. This condition typically occurs sporadically but may also have a familial or autosomal dominant inheritance pattern.

On clinical evaluation, patients with partial sclerocornea have a peripheral, white, vascularized, 1- to 2-mm corneal rim that blends with the sclera, obliterating the limbus. The central cornea is generally normal. In total sclerocornea, the entire cornea is involved, but the center of the cornea is clearer than the periphery. This finding distinguishes it from Peters anomaly, in which the center is most opaque. The opacification affects the full thickness stroma and limits visualization of the posterior corneal surface and of the intraocular structures.

Histopathology reveals disorganized collagenous tissue containing fibrils that is larger than normal. Potential coexisting abnormalities include a shallow anterior chamber, abnormalities of the iris and the lens, and microphthalmos. Systemic abnormalities, such as limb deformities and craniofacial and genitourinary defects, can also accompany this finding. In generalized sclerocornea, early keratoplasty should be considered to provide vision, although the prognosis is guarded.^[1]

Descemet membrane tears

Forceps-induced obstetric trauma, with resultant Descemet membrane tears and corneal edema and clouding, is a cause of corneal clouding. This clouding is differentiated from primary congenital glaucoma (PCG) by the presence of periorbital soft tissue trauma, normal intraocular pressure (IOP), and the frequently vertical orientation of the Descemet membrane tears, and the absence of corneal enlargement, an abnormally deep anterior chamber, and an abnormal filtration angle.

Breaks in the Descemet membrane should be identified and differentiated from other abnormalities, such as the more vertically oriented defects seen after forceps-induced birth trauma or the irregularly scattered defects seen with posterior polymorphous dystrophy.

Corneal edema and haze are common signs of congenital glaucoma, as are horizontal or circumferential breaks in the Descemet membrane (termed Haab striae). Haab striae will remain visible on examination throughout the patient's life, even if the edema resolves with IOP normalization. Gonioscopic findings show a higher, flatter insertion of the iris at the level of the scleral spur, and the trabecular meshwork appears compacted.

Ulcers

Viral keratitis, such as herpetic keratitis or rubella keratitis, can result in a cloudy cornea in the newborn. Rubella keratitis in the newborn may particularly resemble PCG because it can be bilateral and associated with glaucoma.

Metabolic causes

Mucopolysaccharidoses

Mucopolysaccharidoses (MPS) can manifest with corneal clouding, including Hurler, Scheie, and Hurler-Scheie syndromes (all MPS I); Morquio syndrome (MPS IV); and Maroteaux-Lamy syndrome (MPS VI). Corneal clouding is not present in Hunter syndrome (MPS II) and Sanfilippo syndrome (MPS III).

Sphingolipidoses

For the most part, sphingolipidoses affect the retina, not the cornea, except in Fabry disease, an X-linked recessive disease. Fabry disease causes whorl-like opacities in the corneal epithelium (cornea verticillata), similar to those caused by chloroquine or amiodarone. Symptoms of Fabry disease also include skin lesions and peripheral neuropathy; renal failure is a common and serious complication.

Mucolipidoses

Mucolipidoses manifest with corneal clouding, in particular GM gangliosidosis type 1 and mucolipidoses types I and III.

Peters anomaly

Peters anomaly is not an isolated anterior segment abnormality; rather, it occurs as a diverse, phenotypically heterogeneous condition associated with several underlying ocular and systemic defects. Peters anomaly and PCG are genetically and phenotypically distinct conditions.

Central, paracentral, or complete corneal opacity is always present in patients with Peters anomaly. In usual cases, no vascularization of this opacity occurs; this feature helps in distinguishing it from other causes of congenital corneal opacity.

In Peters anomaly, central or paracentral corneal opacity is present. In some cases, this opacity may involve the entire cornea. In type 1, the lens may or may not be cataractous; however, the lens does not adhere to the cornea. In type 2, the lens is cataractous and adheres to the cornea. It is associated with defects in thePAX6 gene.

Congenital hereditary endothelial dystrophy

CHED manifests either in infancy or in young childhood with a cloudy cornea, light sensitivity, tearing, and sometimes nystagmus. An autosomal recessively inherited type of CHED usually appears at birth and is not progressive. Infants with this type of CHED are usually comfortable despite sometimes having profound corneal swelling. A dominantly inherited form of CHED occurs and is generally less severe than the autosomal recessive form in presentation. Youngsters with the dominantly inherited form usually present to the ophthalmologist by 2 years of age, when their parents begin to notice tearing, bright light sensitivity, and sometimes corneal haziness. No other ocular or systemic abnormalities are associated with either form of CHED.^[2]

As stated, CHED is a corneal dystrophy characterized by diffuse bilateral corneal clouding resulting in impaired vision. It is inherited in an autosomal dominant or autosomal recessive manner. The autosomal dominant form of CHED has been mapped to the pericentromeric region of chromosome 20. Another endothelial dystrophy, posterior polymorphous dystrophy, has been linked to a large and overlapping region on chromosome 20.

A large, Irish, consanguineous family with autosomal recessive CHED was examined to determine if the disease was linked to this region. The technique of linkage analysis with polymorphic microsatellite markers amplified by polymerase chain reaction (PCR) was used. In addition, a DNA-pooling approach to mapping of homozygosity was used to demonstrate the efficiency of this method. Conventional genetic analysis in addition to a pooled-DNA strategy excluded linkage of autosomal recessive CHED to the autosomal dominant CHED and large loci for posterior polymorphous dystrophy.^[3]

A clear association between congenital glaucoma and congenital hereditary endothelial dystrophy has been described in 3 patients. This combination should be suspected when persistent and total corneal opacification fails to resolve after bilaterally elevated IOP normalizes.^[4]

Harboyan syndrome

Harboyan syndrome manifests with diffuse bilateral corneal edema and occurs with severe corneal clouding, blurred vision, visual loss, and nystagmus. It is a congenital hereditary endothelial dystrophy (CHED) joined with progressive, postlingual sensorineural hearing loss.

According to Desir, 24 cases from 11 families of various origins (eg, Asian Indian, South American Indian, Sephardi Jewish, Brazilian Portuguese, Dutch, Gypsy, Moroccan, Dominican) have been reported.^[5]

Mutations in the SLC4A11 gene located at the CHED2 locus on band 20p13-p12 cause Harboyan syndrome, demonstrating that CHED2 and Harboyan syndrome are allelic disorders.

Limbal dermoids

Sherman has extensively described limbal dermoids. Limbal dermoids are benign congenital tumors that contain choristomatous tissue (tissue not normally found at that site). They most frequently appear at the inferior temporal quadrant of the corneal limbus. However, they are occasionally present entirely within the cornea or confined to the conjunctiva. They may contain a variety of histologically aberrant tissues, including epidermal appendages, connective tissue, skin, fat, sweat gland, lacrimal gland, muscle, teeth, cartilage, bone, vascular structures, and neurologic tissue (including brain tissue). Malignant degeneration is extremely rare.

The most common system for classifying dermoids is based on their location and separates the lesions into 3 broad categories. The most common dermoid is the limbal dermoid, in which the tumor straddles the limbus. These are usually superficial lesions, but they may involve deep ocular structures. The second type involves only the superficial cornea, sparing the limbus, the Descemet membrane, and the endothelium. The third type involves the entire anterior segment in which the cornea is replaced with a dermolipoma that may involve the iris, the ciliary body, and the lens. Ultrasound biomicroscopy can be helpful in determining the extent and depth of the lesion.

Inheritance is usually sporadic, although autosomal recessive or sex-linked pedigrees exist. They can be associated with corneal clouding.

Although most limbal dermoids are isolated findings, approximately 30% are associated with Goldenhar syndrome, especially when they are bilateral.

Cornea plana

Cornea plana is an extremely rare, congenital hereditary malformation of the corneoscleral shape.^[6]

Corneal keloids

Perry noted, "Corneal keloids are hypertrophic scars of the cornea that may be present at birth following intra-uterine trauma but more often appear spontaneously or after minor trauma in early childhood."^[7] These scars seem to be related to an inappropriate repair response of the corneal tissue to trauma. They are also associated with Lowe syndrome.

OAV dysplasia (Goldenhar-Gorlin syndrome)

Blepharoptosis, bilateral epibulbar dermoids, microphthalmia, epibulbar tumors, and retinal abnormalities have been documented in Goldenhar syndrome. Visual acuity is usually reduced and corneal clouding can occur.

Congenital corneal ectasia

Congenital corneal ectasia is an opaque, ectatic cornea extending between the lids and commonly occurring with corneal and lens clouding.

Congenital hereditary stromal dystrophy

Congenital hereditary stromal dystrophy manifests neonatally with a diffuse clouding of the central anterior corneal stroma with other normal corneal physical and nervous structures. The cornea is not edematous. It is nonprogressive. Its inheritance is autosomal dominant. Visual acuity is decreased. Strabismus and nystagmus may occur. The basic defect appears to be disordered fibrogenesis of stromal collagen.

Posterior polymorphous dystrophy

Posterior polymorphous dystrophy (PPMD) is a slowly progressive, uncommon, dominantly inherited condition. It is usually bilateral but sometimes asymmetric. It manifests with isolated or coalescent posterior corneal vesicular (the most distinctive characteristic), multilayered Descemet membrane thickening, and a bandlike configuration with sharp scalloped margin. It can cause progressive corneal edema and is associated with iris irregularities and glaucoma. Bower has suggested that PPMD might be linked to Alport syndrome.^[8]

Fryns syndrome

First described in 1979, Fryns syndrome is a rare, generally lethal, autosomal recessive multiple congenital anomaly (MCA) syndrome. Patients with the syndrome present with the classical findings of cloudy cornea, brain malformations, diaphragmatic defects, and distal limb deformities.

Pathophysiology

Genetic, developmental, metabolic, and idiopathic factors are implicated as the pathophysiologic basis for congenital clouding of the cornea.

In a 2012 study, 26 children and 37 eyes with congenital cataracts were studied.^[9]Central corneal thickness increased the need for congenital cataract surgery, particularly in younger children, while intraocular pressure was not correlated to increased central corneal thickness.

In a study published in 2013 of 26 patients with primary congenital glaucoma compared with 20 normal controls, corneal hysteresis and corneal resistance factor had a high correlation with central corneal thickness.^[10] Researchers found that in primary congenital glaucoma, keratocyte density measured with vivo laser-scanning confocal microscopy decreased but did not impact corneal hysteresis and corneal resistance factor. In primary congenital glaucoma, mean endothelial density decreased but did not impact corneal hysteresis and corneal resistance factor. The average endothelial density also decreased in primary congenital glaucoma. They concluded that reduced central corneal thickness and increased corneal diameter were major ocular factors relating to the modified corneal biomechanical profile in primary congenital glaucoma, whereas cellular alterations in corneal endothelium and stroma and did not have a substantial biomechanical impact.

The Pbx TALE (three-amino-acid loop extension) homeodomain proteins interact with class 1 Hox proteins and play an essential role in the development of the cornea.^[11]

A common reason for congenital clouding of the cornea is congenital glaucoma.

Peters anomaly has been linked to genetic defects in the PAX6 gene, and a vascular-disruption sequence may be an important pathogenetic mechanism of the anomaly.

Congenital stromal dystrophy of the cornea caused by a mutation in the decoringene has been noted and linked to congenital clouding of the cornea.

New mutations in the beta-crystallin gene occurring in Chinese kindreds with nuclear cataracts have been reported.^[12]

The autosomal dominant disorder Axenfeld-Rieger syndrome is associated with defects in the development of the eyes, teeth, and umbilicus. The eye manifests with iris ruptures, iridocorneal adhesions, cloudy corneas, and glaucoma. Transcription factors, such as PITX2 and FOXC1, carry point mutations that cause the disorder. Findings indicate a novel pathogenetic mechanism in which excess corneal and iridal PITX2A causes glaucoma and anterior defects that closely resemble those of Axenfeld-Rieger syndrome.

Mucopolysaccharidoses (the genetic defects of which have been elaborated elsewhere) are linked to congenital clouding of the cornea. In addition to mucopolysaccharidoses, the differential diagnosis of bilateral corneal stromal opacification includes diseases related to high-density lipoprotein (HDL) deficiency (eg, lecithin-cholesterol acetyltransferase [LCAT] deficiency, Tangier disease, fish-eye disease), Schnyder crystalline stromal dystrophy, cystinosis, gout, and mucolipidoses.

Cloudy cornea can result from congenital infections, such as rubella, and excess prenatal maternal consumption of alcohol.

Lumican and keratocan are members of the small leucine-rich proteoglycan (SLRP) family. They are the major keratan sulfate proteoglycans in the corneal stroma. Both lumican and keratocan are essential for normal cornea morphogenesis during embryonic development and maintenance of corneal topography in adults. This function is attributed to their bifunctional characteristic (protein moiety–binding collagen fibrils to regulate collagen fibril diameters and highly charged glycosaminoglycan [GAG] chains extending out to regulate interfibrillar spacings) that contributes to their regulatory role in extracellular matrix assembly.

In homozygous knockout mice, the absence of lumican leads to the formation of cloudy corneas due to an altered collagenous matrix characterized by large fibril diameters and disorganized fibril spacing. In contrast, keratocan knockout mice have thin but clear corneas with an insignificant alteration of the stromal collagenous matrix. Mutations of keratocan cause cornea plana in humans, which is often associated with glaucoma and corneal opacities.^[13]

Congenital corneal ectasia is thought to be due to a failure of the embryonic mesoderm to migrate and form the corneal endothelium and stroma of the iris at approximately 7 weeks' gestation.

Epidemiology:

Frequency

United States

Corneal clouding, whether idiopathic or linked to a genetic syndrome, is uncommon in newborns.

In a study by Rezende et al at Wills Eye Hospital, among 78 cases of congenital corneal abnormalities, the most common primary cause was Peters anomaly (40%), followed by sclerocornea (18%), dermoid (15%), congenital glaucoma (7%), microphthalmia (4%), birth trauma, and metabolic disease (3%).^[14] Seven eyes (9%) were classified as idiopathic.^[14] Ten patients had systemic abnormalities associated with their ocular condition. Management was medical in 38 eyes (49%). Twenty-four eyes (31%) underwent only 1 penetrating keratoplasty (PK). Only 1 eye received a regraft during the follow-up period. Eight grafts failed during the follow-up period.

Blindness results from corneal opacity and the occasionally associated cataracts and glaucoma. Amblyopia is common. Mortality may be increased because of systemic involvement, especially cardiac anomalies that are systemic manifestations of syndromes that include corneal clouding.

Race

No racial association is reported with the development of corneal clouding.

Sex

No sexual predilection is reported with congenital corneal clouding. However, corneal clouding from keloids is most common in persons with dark skin.

Rupture of Descemet’s membrane and vertical striae :

Descemet’s membrane breaks occur secondary to a variety of conditions that include congenital glaucoma, keratoconus, and trauma. These breaks are classified depending on their time of presentation in early childhood or adulthood, laterality, affecting one or both eyes, and corneal orientation, as vertical, horizontal, or oblique. Descemet’s breaks can be seen in newborns after complicated forceps delivery because Descemet’s membrane is thin and susceptible to stretching at birth [1]. The vertical breaks result from a horizontal stretching of the globe that occurs with vertical compression of the eye between the orbital roof and the blade of the obstetric forceps [2]. These patients can present with decreased vision early in life, secondary to corneal opacification, induced astigmatism, and/or amblyopia, or in adulthood secondary to corneal edema resulting from gradual endothelial decompensation of a previously compromised endothelium [3]. Here we report the clinical history and histopathological correlation of the findings in the stripped Descemet's membrane of a patient who underwent Descemet's stripping endothelial keratoplasty to correct a cornea that failed because of vertical Descemet's breaks associated to forceps injury during delivery.

2. Case Report

A 39 y/o male patient presented with a 2-month history of decreased vision, halos, pain, and photophobia of the left eye. The patient was diagnosed with keratoconus at age 16, for which he used rigid contact lens in the left eye, with a best corrected visual acuity (VA) of 20/60. The patient’s past medical history revealed that he had a complicated vaginal delivery with the use of obstetrical forceps.

Clinical examination showed a VA of 20/400 in the left eye with a refraction of  and a stable VA of 20/20 in the right eye with a refraction of . Slit lamp biomicroscopy displayed corneal stromal and epithelial edema associated with centrally located parallel vertical opaque lines at the level of Descemet's membrane (Figure 1). The right eye had no corneal changes and the intraocular pressure and the posterior segment examination was unremarkable in both eyes. Further studies included a corneal topography (Orbscan) that ruled out keratoconus and showed regular astigmatism of 5.7 D at an axis (097°) that correlated with the location of the striae on slit lamp, and an anterior segment OCT that showed hypereflective linear structures protruding into the anterior chamber at the level of the posterior cornea.

Figure 1: Slit lamp photo showing corneal edema and vertical opaque lines at the level of Descemet’s membrane.

A diagnosis of corneal edema secondary to endothelial decompensation in the left eye secondary to forceps injury and history of Descemet’s membrane break was made. The patient underwent a Descemet’s stripping automated endothelial keratoplasty (DSAEK) in order to replace the diseased posterior corneal lamella that included a Descemet’s membrane previously traumatized by the obstetrical forceps, and an endothelium that had undergone gradual decompensation. The stripped Descemet’s membrane was submitted for histopathological evaluation. The patient had good visual outcome after DSAEK with BCVA of 20/80. Slit lamp examination revealed a well appositioned graft, and a clear cornea with minimal superficial scarring (Figure 2). Mild superficial corneal scarring and preexisting amblyopia limited final visual acuity.

Figure 2: Slit lamp biomicroscopy photo at 1.5 years after DSAEK showing a nonedematous cornea with minimal superficial scarring.

Histological examination of the stripped Descemet's membrane revealed endothelial attenuation and a thickened PAS-positive membrane with areas of nodular thickening at the edge of the initial break composed of concentric deposits of PAS-positive material (Figure 3).

Figure 3: Histopathology of the stripped Descemet’s membrane demonstrating an area of nodular thickening of Descemet’s membrane composed of concentric scrolls of PAS-positive material (periodic acid-schiff stain, original magnification x400).

3. Discussion

The clinical history and histopathological findings in the stripped Descemet's membrane of a 39 y/o patient that underwent DSAEK to treat an endothelial decompensation associated to vertical Descemet's membrane breaks that occurred after obstetrical forceps delivery are reported. The initial Descemet’s membrane rupture causes an acute corneal edema shortly after birth that typically clears over the next few weeks at which time vertical or oblique striae are seen clinically representing permanent linear thickening of Descemet’s membrane at areas of prior breaks [4]. These striae may cause decreased vision secondary to induce astigmatism, high myopia, glare, visual opacification, and amblyopia. In this case, the patient had 5 cylinders of astigmatism with an axis corresponding to the axis of the break that is similar to previous reports that described a mean cylinder of astigmatism of 6.9 D (3.0–10.50 D) in the affected eye compared to 0.36 D (0.0–1.50 D) in the noninvolved eye, with a steep axis parallel to that of the breaks [4]. Patients can also present many years later with corneal edema resulting from endothelial decompensation of a previously compromised endothelium. The patient reported presented with corneal edema secondary to endothelial decompensation at age 39, which correlates with the reported mean time of 37 years (range: 25–44) for clinically significant endothelial decompensation after the initial injury [5, 6].

Honig et al. [5] in 1996, classified the histological findings of Descemet’s breaks in transplanted corneal specimens secondary to forceps injury into four categories: type 1 had a scroll at one margin and a fragment of Descemet’s membrane extending into the anterior chamber at the other margin; type 2 had scrolls of Descemet’s membrane at both margins of the tear; type 3 had fibrous proliferation around the area of break creating a retrocorneal membrane; type 4 contained a small discontinuity in Descemet’s membrane with minimal fibrosis. This case resembles a type 1 injury as we noted a scroll of Descemet’s membrane at one margin of the break on the submitted Descemet’s membrane after DSAEK. The histological finding of scrolls and nodular thickening of Descemet’s membrane seen at the edge of the original breaks are a result of a healing response from the corneal endothelium that laid down many layers of new basement membrane in order to cover the defect [5, 7]. These findings correlate clinically with the striae and ridges noted on exam.

In this paper we demonstrate the use of DSAEK in the management of corneal breaks secondary to forceps injury and show that surgery was successful in removing the affected area of Descemet’s membrane as seen in Figure 3. In addition, for the first time we demonstrate that that this type of injury can be diagnosed histopathologically many years later, with the submission of the striped Descemet’s membrane at the time of DSAEK.

ITCHING EYE :Itching is the hallmark sign of SAC or PAC. Your patients' eyelids are swollen, and their eyes are red, chemotic and watery. Scrapings show elevated eosinophils. Whether the problem is seasonal (pollens) or perennial (dust mites, animal dander and mold), your patients' allergies are causing ocular surface inflammation and maddening discomfort.

Ocular allergies result in swollen eyelids and red, chemotic watery eyes.

Allergies cause mast cell degranulation and the release of histamines and proinflammatory mediators. Therefore, the most effective medications will address both problems.

The allergic reaction is triggered by antigens, which cross-link with the immunoglobulin E antibody (IgE) on the mast cells, leading to mast cell degranulation. This, in turn, releases histamines and proinflammatory mediators, such as prostaglandins, tryptase and heparin. The histamine quickly binds with H1 receptor sites on the nerves and causes itching. It also binds to H1 receptor sites on the blood vessels, causing redness, chemosis and fluid leakage. The proinflammatory mediators only add to the redness and swelling, and there's no end in sight, because antigens continue to bombard the eyes as part of the inflammatory cascade.

Dual effects

If we follow the etiology of allergic conjunctivitis, we can discern some important information. With 50 million mast cells in the human conjunctiva, the mast cell is central to the ocular allergic response. Allergies cause mast cell degranulation and the release of histamines and proinflammatory mediators. Therefore, the most effective medications will address both problems and will rapidly relieve symptoms.

Antigens that cross-link with the IgE antibody on the mast cells trigger the allergic response. This leads to mast cell degranulation and the release of histamines and proinflammatory mediators.

An antihistamine's mechanism of action is simple. It's attracted to the same H1 receptor sites that histamine seeks. It binds to those sites, effectively blocking the attachment of histamines and preventing itching and redness. Clearly, it's beneficial to put an antihistamine to work early in the inflammatory process.

We also need to use a mast cell stabilizer to effectively treat ocular allergy. These drugs prevent recurrence of the allergic response by inhibiting the release of proinflammatory mediators.

Study results

The most commonly prescribed drugs for ocular allergies are olopatadine 0.1% (Patanol, Alcon), olopatadine 0.2% (Pataday, Alcon), epinastine (Elestat, Allergan), ketotifen fumarate (Zaditor, Novartis Ophthalmics) and azelastine (Optivar, Meda Pharmaceuticals Inc.).

Olopatadine 0.1% is the market leader because studies have shown it's clinically effective as a specific H1 antagonist and mast cell stabilizer. It has a quick onset of action, and it's been shown to be comfortable and safe for patients.^1–11

In a conjunctival allergen challenge (CAC) study, which compared olopatadine 0.1% to azelastine⁵ and epinastine¹¹, mean itching scores at 5 minutes were better for olopatadine with statistical significance. The drug also performed better in ocular redness at onset and 10, 15 and 20 minutes post-challenge. Another study showed that olopatadine was significantly more comfortable in the eye than azelastine.⁶

While results are satisfying, another factor has driven the development of another olopatadine formulation: olopatadine 0.2%. Some studies show overall improvements in adherence, patient quality of life, patient satisfaction and cost when patients can dose less frequently.¹² What's more, 95% of allergy patients say that a long-lasting allergy medication is important, so they may be more satisfied if they can use fewer drops.¹³

A once-a-day drug like olopatadine 0.2% could improve compliance over olopatadine 0.1%, and increased compliance through daily dosing has been shown to give patients better symptom control.¹² In an in vitro animal comparison of the two concentrations, olopatadine 0.1% lasted 14 to 15 hours, compared to 24 hours for olopatadine 0.2%.¹⁴

Newest option

Indicated for the treatment of ocular itching associated with allergic conjunctivitis, olopatadine 0.2% has the same safety profile as olopatadine 0.1%. Olopatadine 0.2% has an increased concentration and longer duration, which is why patients need to use it only once a day.^15,16

An antihistamine is attracted to the same H1 receptor sites that histamine seeks. It binds to those sites, effectively blocking the attachment of histamines, thereby preventing ocular itching and redness.

During in vitro studies, both doses of olopatadine thwarted the biphasic process that degranulates mast cells and releases mediators, while epinastine, azelastine and ketotifen did not.^17,18

In more than 10 clinical trials, more than 1,000 patients have been exposed to olopatadine 0.2%. In a randomized, double-masked, placebo-controlled CAC trial¹⁹ that studied 45 people with a history of allergic conjunctivitis, researchers checked patients for itching and redness at onset and after 24 hours. They found that olopatadine 0.2% significantly reduced ocular itching compared to placebo. In the same study, researchers also found a beneficial effect on conjunctival redness.

A multicenter, 10-week study²⁰ looked at the efficacy of olopatadine 0.2% against itching in 260 patients who were sensitive to grass pollen and experienced redness and tearing. They received 1 drop in each eye, once a day. In weekly assessments, patients rated olopatadine 0.2% significantly better than placebo in itching frequency. What's more, the results improved over time as the mast cell stabilizer had time to take effect. Ocular redness fared better than placebo in the same 10-week period.

In addition, the environmental study showed that 0.2% olopatadine was effective, even as allergen levels fluctuated from low to moderate.²⁰

In comparative drug studies, olopatadine 0.2% has continued to fare well. In the double-blind CAC trial²¹ against epinastine, 92 patients underwent screening, confirmation and an office visit.

Results showed that olopatadine 0.2% reduced itching and redness more effectively than epinastine and also scored well in the comfort comparison index.

Indicated for the treatment of ocular itching associated with allergic conjunctivitis, olopatadine 0.2% has the same safety profile as olopatadine 0.1%, [but offers] an increased concentration and longer duration.

                         Strabismus

Strabismus, more commonly known as cross-eyed or wall-eyed, is an eye muscle condition in which one or both eyes may turn in (esotropia), out (exotropia), up (hypertropia) or down (hypotropia).

The eyes are not properly aligned and do not focus on an object together at the same time. One eye may be turned all of the time or only some of the time. Most people who have strabismus are usually born with it or develop it at an early age. However, some forms of strabismus occur later in life.

Symptoms:

Newborns often have crossed eyes to some degree due to underdeveloped vision, but this usually disappears by the age of 3 to 4 months. True strabismus does not disappear as the child grows. If you think your child is showing signs of true strabismus, it is important to seek the advice of an eye care professional. The earlier the detection and treatment, the better the child's vision will be. Symptoms to watch out for include:

• Eyes that appear crossed
• Eyes that do not align in the same direction
• Eyes that do not move together
• Double vision
• Vision in only one eye, with loss of depth perception

Causes:

Strabismus is caused by a weak eye muscle or a weak signal from the nerve that controls the eye muscle. Frequently, uncorrected farsightedness and focusing problems are the underlying causes of strabismus in children. Some children are born with a defective visual processing center in the brain. Strabismus may also develop if a child is born with a cataract. It is common in conditions such as Down’s syndrome and cerebral palsy. Bleeding in the brain, a brain tumor, nervous system disorders, diabetes, high blood pressure, myasthenia gravis, thyroid disease and severe vision loss can also cause strabismus.

Risk factors:

One of the highest risk factors for strabismus is having a family history of strabismus. Having a moderate to high amount of farsightedness at a young age can also increase the risk significantly, as does having a disease such as diabetes or high blood pressure. In addition, strabismus may develop as a complication of any other disease causing vision loss.

Types:

Strabismus is categorized as being either constant (turned in all of the time) or intermittent (turned in some of the time). Cases of crossed-eyes, or esotropia, are classified as either "congenital" or "accommodative" esotropia.

• Congenital esotropia: An uncommon condition in which a baby is born with an inward turn of a large amount, usually appearing between the ages of 2 and 4 months.
• Accommodative esotropia: An inward turning eye that occurs because the eye is attempting to compensate for uncorrected farsightedness or a focusing disorder.

• Diagnosis:

  Besides parents, a pediatrician or family doctor is often the first person to detect strabismus. A baby whose eyes do not appear straight by the age of 3 to 4 months should be examined. To properly diagnose strabismus, a complete eye examination must be performed by an eye doctor. Early diagnosis is very important, as some eye turns may be a result of a serious medical condition. Strabismus that is not treated early in a child’s life may cause amblyopia (lazy eye), a condition in which vision develops poorly. In addition, the cosmetic appearance of strabismus may cause a lack of self-esteem.

  Treatment:

  Strabismus cannot be outgrown. Treatment to straighten the eyes is required. Treatment will depend on the type of strabismus and its cause:

  • Glasses may be prescribed to improve focusing and enable the eyes to straighten.
  • Patching the good eye will force a patient to use the affected eye. Patching will improve the chances of normal vision to develop.
  • Eye drops may be used to blur the good eye, forcing the affected eye to be used. (This achieves the same result as patching.)
  • Eye muscle surgery may be an option if non-surgical treatments do not work.
  • Some eye doctors may prescribe eye exercises before or after surgery.
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  •                   Albinism  Child's Eyes

    If your child has just been diagnosed with albinism, you may be wondering how the condition might affect his eyes and vision. Albinism is an inherited disease that can affect both the eyes and the skin, but sometimes it only affects the eyes. People with albinism typically have little to no pigment in their skin and hair.

    Albinism can sometimes have profound effects on vision and eye health. The disease can affect the amount of pigment present in the back of the eye as well as the development of the neural connections between the eyes and the brain, causing problems such asnearsightedness, astigmatism, light sensitivity, and glare. Fortunately, eyeglasses may significantly improve your child's overall eye problems.

    Albinism and Eye Color

    Children with albinism usually have blue eyes, but some have brownish-colored eyes. Some children will even appear to have pink or red eyes, because the iris doesn't contain much pigment. The pinkish color results due to a lack of pigment in the iris. The inside of the eye will also appear very light because the eyes lack the pigment that is contained in the layer directly beneath the retina.
    

    Albinism and Refractive Errors

    Children with albinism tend to be nearsighted or farsighted and often have large amounts of astigmatism. Glasses or contact lenses can be used to correct these vision problems.

    Albinism and Light Sensitivity

    Children with albinism can have profound light sensitivity. In a normal eye, the iris helps to shield the retina from bright light. When a child has albinism, their iris is sometimes so light in color that it can't properly control the amount of light that hits the retina. Also, because the back of the eye also lacks pigment, light is not absorbed properly and scatters, creating more light sensitivity. These children require sun protection, including quality sunglasses or tinted contact lenses.

    Some children with albinism may benefit from a permanent tint in their prescription eyeglasses that is light enough to function indoors. Children with albinism may also benefit fromphotochromic lenses. Photochromic lenses darken to a grey or brown shade when in sunlight and automatically lighten back to clear indoors. Many different types of photochromic lenses are available today and they may benefit from photochromic lenses that turn darker outside but do not necessarily lighten up completely when indoors. They remain slightly tinted indoors.

    Albinism and Glare

    Glare is light that is reflected off surfaces such as water, waxed floors and white sand. Glare can make even the cloudiest day uncomfortable for children with albinism. Because glare can be debilitating to these children, polarized sunglass lenses are highly recommended. Polarized sunglasses reduce not only the amount of light that enters the eye but they also virtually eliminate associated glare. Polarized lenses can make children with albinism much more comfortable and deliver a much better visual experience for them. Polarized lenses are available in many different colors and are available in both constant tints and photochromic options.

    To further enhance comfort for children with albinism, many doctors and opticians recommend adding a mirror coating to their sunglass lenses. A mirror coating will reduce the amount of light that reaches the eyes even further and deflect the light that bounces up and enters the eye from below.

    Albinism and Other Vision Problems

    Children with albinism may also develop other vision problems that will require attention, such as nystagmus and strabismus. Nystagmus is an involuntary flicker of the eyes. Nystagmus usually causes a child to make quick, jittery movements by both eyes. Strabismus is an eye muscle condition that causes one or both eyes to turn in, out, up or down.
    

               Vision Screening for Kids

    
    

    An evaluation of your child's eyes should occur at all well child visits, even as an infant.

    Routine vision screening is important, because many abnormalities are treatable if discovered early, and untreated, can lead to vision loss and blindness. Among the vision problems that your Pediatrician will evaluate your child for include:

    • strabismus - a misalignment of the two eyes, affecting about 4% of children. Strabismus is usually described by the direction of misalignment, which can be outward (exotropia), inward (esotropia), upward (hypertropia) or downward (hyotropia). A child may also have a phoria, with eye deviation only when one of the eyes is covered or when he is tired or sick.
    • amblyopia - reduced vision in an eye, which can be secondary to strabismus, anisometropia (unequal refractive errors in both eyes, for example, if one eye is more farsighted than the other eye), congenital cataracts, etc.
    • refractive errors - such as myopia (nearsightedness) and hypermetropia (farsightedness).

    In younger children, a vision evaluation will usually consist of an examination for the red reflex (checks for cataracts and retinoblastoma), eye alignment (misaligned eyes may indicate strabismus) and eye movements. Older children, beginning at three years of age, should have a more formal test of their vision. Until formal vision testing is possible after three years of age, younger children's vision can be assessed by observation of how they fixate and track objects and by the history of the child's parents. Visual milestones for infants include being able to follow an object to midline in the first 2-6 weeks, past midline by 1-3 months, and follow an object 180 degrees by 3-5 months. If your child isn't meeting these developmental milestones on time, then you should see your Pediatrician for an evaluation.

    
    

    Other testing may include the corneal light reflex test, in which a light is directed at the bridge of the nose and the light reflex is examined to make sure it is symmetrical or shines in the same spot on both eyes. If the light reflex is off-center or not symmetrical in both eyes, then it might indicate a misalignment of the eyes. This is useful to differentiate pseudostrabismus, a condition in which the eyes appear to be misaligned because of prominent epicanthal folds or a broad nasal bridge and which doesn't require treatment, from true strabismus.

    The unilateral cover test can be used to determine if an infant or young child will follow an object while one of the eyes is covered. For example, your Pediatrician can see if your child can fix on and follow a toy with both eyes, and then cover the left eye and see if he continues to follow it with his right eye. Then, the right eye is covered to see if he will follow the toy with his left eye. If he gets really fussy or refuses to follow the object when you cover one of his eyes, then that may indicate that the vision in the other eye is reduced.

    In older children, the unilateral cover test is also useful to check for strabismus. While the child is looking at a distant object, such as an eye chart or toy, cover one of his eyes. If the other eye moves outward or inward, then that might indicate that his eyes are misaligned and that he has strabismus. The test is then repeated by covering the other eye.

    Other problems that indicates the need for further evaluation include parents noticing that their child's eyes are crossing, that their eyes aren't straight or if they just don't seem to be seeing well. It is important to keep in mind that younger children usually don't report problems with their vision, especially if the problem is in just one eye and the other eye is accomodating for it. Older, school age children, may report that they can't see the board, or they may have frequent headaches, double vision or are frequently squinting. Formal testing of visual acuity is usually possible once a child is three years old, although 2 year olds may be able to be tested with picture cards

    
    

    
    

Dr.kalpana.

infection

Herpes simplex virus (HSV) is the most common infectious cause of corneal blindness in the Western Hemisphere, with up to 500,000 cases diagnosed annually in the United States alone. HSV is a multifaceted disease capable of inducing some of the most difficult management problems, including neurotrophic keratopathy. Herpetic neurotrophic keratopathy often presents with decreased corneal sensation and significantly impairs the ability of the corneal epithelium to heal itself after corneal injuries, leading to corneal ulcers in the absence of active virus. Neurotrophic keratopathy can also develop after Herpes Zoster (shingles) which leads to chronic epithelial disease and loss of vision. The persistence of decreased corneal sensation and its association with the degree of nerve damage in the cornea are still unknown.
In collaboration with Dr.Kalpana professor  of Ocular Virology, we are currently studying the nerve changes and cellular changes in herpetic disease. Through the use of the new state of the art HRT/RCM confocal microscope, which allows a revolutionary layer-by-layer analysis of the cornea and a magnification of up to 800 times, we are able to perform non-invasive examination of the cornea and obtain images of corneal layers and cells.

Treating the Ocular Component of Allergic Rhinoconjunctivitis and Related Eye Disorders:

D.RAJESH DODDAA range of treatment options are available for the control of ocular allergy symptoms, some of which may obviate pharmacologic interventions . Allergen avoidance is implemented by minimizing patient contact with the allergens to which they are sensitive; however, the eyes present a large surface area and thus it is often impossible or at least impractical to avoid ocular exposure to airborne allergens. Allergens can also be diluted and removed from the ocular surface through lubrication with artificial tears (saline combined with a wetting and viscosity agent); however, the unit-dose packaging required for sterility makes these products expensive, and they do not treat the underlying allergic response. Cold compresses are another nonpharmacologic intervention that may provide relief from ocular symptoms.

When avoidance and nonpharmacologic strategies do not provide adequate symptom relief, pharmacologic treatments may be applied topically or given systemically to diminish the allergic response. For example, the H ₁ topical antihistamine levocabastine hydrochloride is effective in rapidly relieving ocular inflammation when administered topically to the eye.  However, a limited duration of action necessitates frequent dosing of up to 4 times per day,  and topical antihistamines may be irritating to the eye, especially with prolonged use. Because atopy has been shown to be related to a fivefold increase in symptoms during allergy seasons, patients who use contact lenses should consider the use of soft daily-disposable lenses for comfort.  A small percentage of patients may have to discontinue the use of contact lenses during acute periods.

Combination treatments using decongestants with antihistamines have been shown to be more effective, and are administered to the eye as drops up to 4 times daily. Decongestants (oxymetazoline hydrochloride, tetrahydrozoline hydrochloride, and naphazoline hydrochloride) act primarily as vasoconstrictors and are effective in reducing erythema  ; however, adverse effects include burning and stinging on instillation, mydriasis, and rebound hyperemia or conjunctivitis medicamentosa with chronic use. Therefore, these treatments are suitable only for short-term symptom relief, and are not recommended for use in narrow-angle glaucoma patients.

Mast-cell stabilizing medications (cromolyn sodium 2% or 4%, lodoxamide tromethamine 0.1%, nedocromil sodium 2%) can also be applied topically to the eye, and may be suitable for more severe forms of conjunctivitis. However, for mast-cell stabilizers to be effective, the mast cell has to be de-activated before the allergic reaction is triggered, thus they require a loading period during which they must be applied before the antigen exposure. Compliance is, therefore, an important factor because frequent regular dosing before an allergic reaction can become difficult for patients to adhere to. Cromolyn sodium is used in several types of conjunctivitis, including forms of AC; however, studies have shown only marginal effectiveness compared with placebo.  Lodoxamide tromethamine is more potent than cromolyn sodium in the prevention of histamine release in animal models,  and has been shown to provide relief from the symptoms of VKC. Nedocromil sodium has also been shown to be more potent than cromolyn sodium. 

In contrast to classical mast-cell stabilizers, the topical antihistamine mast-cell stabilizers have a dual mode of action: they inhibit mast-cell degranulation while competitively blocking histamine binding to H ₁receptors, thus providing rapid allergic symptom relief through antihistamine action. As a result of this more rapid action, compliance is likely to be greater compared with that of the pure mast-cell stabilizers. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are possible candidates for treating the symptoms of SAC. The only NSAID currently approved for SAC is ketorolac tromethamine 0.5%, which works on the arachidonic acid cascade and is effective in reducing ocular itching. However, as is the case for several classes of topical ocular treatments, NSAIDs are also known to cause discomfort on instillation,  which may affect patient compliance.

The more severe variants of conjunctivitis, including AKC, VKC, and GPC, can be controlled by topical corticosteroids (loteprednol etabonate 0.2% and rimexolone 0.1%), which are also effective in the treatment of acute and chronic forms of AC. . Corticosteroids administered via eye drops are associated with serious adverse events when administered over long periods, including increased intraocular pressure (IOP) and cataract formation, and these agents are therefore appropriate for short courses (up to 2 weeks); however, if needed for longer durations, an eye examination should be carried out, including baseline assessment of cataracts and IOP. 

The topical ocular treatments described above share common limitations that arise from the mode of administration. Many adults have poor tolerance of eye drops, and they are particularly difficult to administer in a sterile manner when patients suffer from arthritis or tremors, or when used in pediatric practice. Since eye drops are cleared rapidly from the eye, efficacy and duration of action may be reduced, necessitating frequent administration and increasing expense. Moreover, compliance is a major issue in the use of eye drops,  which may be exacerbated by allergies that affect multiple systems. Patients may need to use a nasal treatment plus oral antihistamines, and topical creams and inhalers. It may be beneficial to reduce the number of agents used regularly by a patient through the use of immunotherapy, and orally or nasally administered allergy treatments that are effective against ocular symptoms. 

The efficacy of immunotherapy against ocular symptoms precipitated by conjunctival antigen challenges was originally demonstrated in 1911,  and this well-established method may be considered for the long-term control of AC. Although some more recent studies have focused on nasal rather than ocular symptoms,  others have confirmed the efficacy of immunotherapy against ocular symptoms. However, immune responses to allergen administration are not predictive of the effectiveness of the therapy,  and the therapy itself can produce systemic reactions, the incidence and severity of which vary dependent on the type of allergen administered.  Traditionally, immunotherapy has involved subcutaneous administration of allergen solution; however, newer sublingual immunotherapy (SLIT) provides a more convenient option. SLIT requires further evaluation for ocular allergy relief; it has been shown to control ocular signs and s ocular symptoms may respond less well than nasal symptoms. 

Oral antihistamines (cetirizine hydrochloride, desloratadine, fexofenadine hydrochloride, and loratadine) are commonly used for the therapy of nasal and ocular allergy symptoms. These newer second-generation antihistamines are recommended in preference to first-generation antihistamines because they have a reduced propensity for adverse effects such as somnolence.  Loratadine has been shown to have a protective effect in conjunctival provocation tests,  and desloratadine and fexofenadine hydrochloride have been found to significantly reduce ocular symptoms of SAR in placebo-controlled studies. In addition, cetirizine has demonstrated efficacy against symptoms of AC in conjunctival provocation tests;  however, a double-blind placebo-controlled trial showed no impact on ocular symptoms of perennial allergic rhinitis (PAR).  Second-generation antihistamines can, however, induce ocular drying,  which may impair the protective barrier provided by the ocular tear film and thus actually worsen allergic symptoms. It has therefore been suggested that the concomitant use of an eye drop may treat ocular allergic symptoms more effectively.  Indeed, ketotifen fumarate plus desloratadine,  and olopatadine hydrochloride plus loratadine have been shown to be more effective than either antihistamine alone as a result of the local effect of the topically applied agent. In addition, one trial has shown that eye irritation was significantly reduced by an antihistamine preparation that had been formulated for intranasal application (azelastine hydrochloride).  However, these results have been inconsistent because eye watering was significantly reduced compared with placebo by twice-daily (but not once-daily) application of azelastine hydrochloride in 1 trial,  but was not significantly reduced in another. 

Intranasal corticosteroids (INS) are highly effective for treating nasal symptoms of AR,  but the evidence that they may also be effective for the treatment of ocular symptoms is inconsistent. Currently, the mechanism by which intranasal treatments act on ocular symptoms is not known. Potential mechanisms include improved drainage of ocular secretions resulting from a reduction of edema and inflammation around the lower end of the nasolacrimal duct, and a decrease in neuronal reflex activity. It is well established that allergen challenges to one side of the nasal cavity lead to nasal secretion in the contralateral cavity via a neurologic reflex. Nasal challenges have also produced ocular itching in 90% of patients in 1 study,  and ocular symptoms in approximately 20% in another, suggesting that ocular symptoms may be induced by a nasal-ocular reflex . It may be the case that INS inhibit the nasal-ocular component of ocular allergy symptoms, but not the direct ocular component.

The variation in effectiveness of INS on ocular symptoms may therefore be the result of varying levels of affinity for nasal receptors. Systemic effects are unlikely with these agents as they have low bioavailability and rapid first-pass metabolism leading to low plasma levels.  Thus, the amount of an intranasal steroid available in the eye for a direct therapeutic effect is miniscule. Passage of agents from the nose to the eye via the nasolacrimal duct has also been shown to be unlikely.  A number of large clinical trials have investigated the ocular efficacy of INS in allergic patients; a meta-analysis of 16 randomized controlled trials showed that INS were more effective against several nasal symptoms of AR than oral antihistamines, and also found no difference in efficacy against AR ocular symptoms between the treatment classes.  Similar conclusions were drawn by a systematic review that determined that 9 of 10 AR studies showed no difference in efficacy for ocular symptoms between INS and oral antihistamines, while 1 study showed superiority of the oral antihistamine.  In contrast, pooled efficacy data from 7 multicenter, randomized, double-blind, placebo-controlled studies have shown that the INS fluticasone propionate 200 mcg once daily provides effective relief of ocular symptoms associated with SAR.  In accordance, a randomized, double-blind, parallel group study conducted at 14 investigative sites showed that fluticasone propionate 200 mcg once daily significantly decreased the ocular symptoms score compared with vehicle placebo however, other placebo-controlled trials found no effect of fluticasone propionate on eye symptoms in adults  or children  with SAC.

Another nasally administered corticosteroid, triamcinolone acetonide, has also been shown to have efficacy against ocular symptoms; however, only 1 placebo-controlled trial showed a statistically significant improvement, and these findings have not been consistent.  Similarly, a pooled analysis of 4 studies found that mometasone furoate 200 mcg once daily may also provide relief from ocular symptoms in patients with SAR. In a recent study, ciclesonide did not have a significant effect on non-nasal symptoms, or the eye symptom domain of the RQLQ.

Ocular allergies, which are often underdiagnosed, have a significant impact on the life of the patient. These symptoms are expensive in terms of treatment and also in terms of indirect costs. It is vital to reach a better understanding of allergic mechanisms and inflammation, which may lead to improved treatment. Moreover, the emergence of new medications for the treatment of nasal and ocular symptoms may improve compliance in patients suffering from allergic conditions, such as AR, in which the ocular component is present. Currently, the most effective treatments for AR are INS; it would be advantageous, therefore, to develop a drug of this class that is consistently shown to improve eye symptoms (as well as nasal symptoms) to provide greater symptom relief, increase patient compliance, and reduce costs associated with the current requirement for multiple medications.

D.RAJESH