Pterygium and its management

Dr Jyoti Prakash Behera

Anatomy of conjunctiva

Histology of normal conjunctiva

Pterygium- Definition

• Derived from Greek word “Pterygos” means small wing

• It is a non malignant slow growing proliferation of wing shaped fibrovascular tissue.

• Arises from subconjunctival tissue.• May extend over the cornea thus disturbing

the vision.

Pterygium- Incidence & Prevalence

• Cameron's map- Shows a direct relationship between prevalence and proximity to the equator(warm and dry climate)

• Factors other than geographic location– Male : female= 2:1– more common in farmers than in city dwellers– more who do not wear eyeglasses– elderly have the highest prevalence rate, but a much

younger (20-to 40-year old) group has the highest incidence rate

• In India prevalence is 9.5%.• Morbidity: causes significant alteration in

visual function in advanced cases.

ETIOPATHOGENESIS.

• Strong association between UV light exposure and formation of pterygium.– More common- in patients who worked outdoors.– In welders than other factory workers.

• Also associated with basal cell carcinoma, porphyria cutanea tarda, polymorphous light eruptions, xeroderma pigmentosa.

• ANGIOGENESIS FACTOR-(Wong) Prolonged UV

exposure causes biological changes in the

bowmans membrane

• UV Exposure: May induce hyperplasia in

limbal cells. These altered cells invade the

cornea and limbus which moves centripetally

with them

ALBEDO HYPOTHESIS

• Light entering the temporal limbus at 90degree is

concentrated at medial limbus (supported and

demonstrated by Coroneo)

• Related to corneal curvature.

• This explains the predominance of medial

pterygium.

Other theories

• Scarpa, Friede, and Kamel believed that chronic inflammation in the form of conjunctivitis or episcleritis initiates the process

• MICROTRAUMA: mechanical irritation by dust particles, enhanced by tear flow from lateral to medial.

• IMMUNOLOGY: Cell bound IgE irritant complexes initiate the release of inflammatory mediators from mast cells→ Release of stimulatory factors→Development of pterygium.

• HYPOXIA: increase in non perfusion areas and attenuated vessels in nasal limbus during early stage of pterygium causes recruitment of progenitor cells.

• Viral markers: infection with HPV and herpes virus is considered as risk factor(rare).

Genetic predisposition

• Expression of vimentin.• P53 mutation leads to decreased apoptosis

and increased TGF-b which leads to increased growth.

Pterygium- Degenerative or proliferative ???

• long been considered a chronic degenerative condition• Classically described as“elastotic degeneration”• Cˇilanova-Atanasova ascertained that the degenerative

or dystrophic changes in pterygium were simply more pronounced than normal aging conjuctiva

• In addition, pterygium tissue had proliferative components that included epithelial hyperplasia and the appearance of newly formed connective tissue, blood vessels and fibrous elements

• Cameron- showed the evidence of transformed, invading subconjuctival fibroblasts that grows centripetally

• Austin and co-workers suggested- excessive production of elastin material by actinically damaged, proliferative subconjunctival fibroblasts

• Primary Pterygium is definitely locally invasive• Also pterygium epithelium exhibits varying degrees

of abnormality, ranging from mild dysplasia to carcinoma in situ

Limbal Stem Cell Deficiency and Epithelial Abnormalities

• Kwok- propose that the initial biologic event in pterygium was an alteration of limbal stem cells due to chronic UV light exposure, resulting in concomitant breakdown of the limbal barrier and subsequent conjunctivalization of the cornea

• primary and recurrent pterygia exhibit overexpression of the p53 tumor-suppressor gene

• Presence of abberant apoptosis

Pterygium-Histopathology

• Three basic elements characterize the histologic appearance

1. Epithelial covering of atrophic conjuctiva extends beyond2. Degenerated connective tissue- a bulky mass of

thickened, hypertrophied, and degenerated connective tissue– collagen component of which assumes a coiled, fibrillated

pattern reminiscent of elastic tissue– The abnormal collagen shows basophilia and an affinity for

elastic tissue stains, but is not digested by elastase– hence categorized as elastotic degeneration

Histology

Normal conjunctiva Pterygium

Histology

3. Vascular element- New blood vessels, usually congested, are dispersed among the hypertrophied collagen fibers

• The episcleral bed beneath the pterygium is hyperemic

• Tenon’s capsule is incorporated into the body of the pterygium and contributes to its vasculature and bulk

Histopathology cont..

• Immediately in front of the head of the pterygium, an advancing row of fibroblasts penetrates the cornea between Bowman’s layer and the basement membrane of the epithelium (grey zone or cap)

• Eventually tissue enters the cornea, Bowman's layer is pushed posteriorly and eventually becomes fragmented

Formed pterygium- schematic

Pterygium- Clinical feature

• A pterygium appears as a fleshy triangular band of fibrovascular tissue

• axis of the triangle gently slopes superiorly on the corneal side

• It has several components– The cap– The head– The body– The base – Superior edge– Inferior edge

• The cap– The cap is a flat, grayish white avascular zone of

variable size located in the subepithelial corneal tissue

– Sometimes a round, gray, coin-like extensions of the cap precede it (“islets of Fuchs")

– some cases, a golden-yellow iron line may be seen (Stocker's line)

– Between the head and the cap there are small capillaries

Stocker's line

Islets of Fuch’s

• The head– It is slightly elevated and white – It is the one site of firm

adhesion to the globe

• The body– fleshy sheet of pink, highly

vascularized tissue– delineated from the normal

conjunctiva superiorly and inferiorly by sharp folds

– frequently reveals punctate staining over the epithelial surface of the body

• Clinical Grading of pterygium

• As proposed by Donald T H Tan

• Grade T1(atrophic)- pterygium in which episcleral vessels underlying the body of the pterygium were unobscured and clearly distinguished

• Grade T3(fleshy)- thick pterygium in which episcleral vessels underlying the body of the pterygium are totally obscured by fibrovascular tissue

• Grade T2(intermediate)- All other pterygia that do not fall into these two categories

• Surgical recurrence correlated well with translucency– fleshy pterygium having the highest capacity for

recurrence– Atrophic has the lowest

Clinical staging of pterygiumCLINICAL STAGING PATHOLOGICAL

STAGINGStage I Exposure

conjunctivitis Size and number of Conjunctival vessels Mild – moderate congestionS/S of drynessNo formed lesions

Altered tear filmMild vascular response

Stage II Pinguecula and pterygium

Distinct raised lesion on bulbar conjunctivaWith or w/o abnormal vascularization and inflammation

Cell injuryInflammatory response

Stage III Limbal pterygium Head is on or across the limbus with or w/o an iron line at the conjunctival corneal interface

Vascularization and fibrous proliferationSymptoms more pronounced

Lesion organization

Mixed proliferation and degeneration

Stage IV Corneal pterygium Lesion 2mm or more into corneaInvasion of granulation tissueZone of dellenStocker’s lineInfiltration of corneal nerves- pain

Lesion b/w epithelium and bowman

Mixed proliferative and degeneration

Stage V Compound pterygium Induced astigmatismSymptoms more frequent and severe

Lesion extended into stroma

Mixed proliferative and degeneration

Proliferation- Small lymphocytes and plasma cellsDegeneration- Swirls of type I collagen

Other types

• Primary double pterygium.

• Recurrent pterygium.

• Pseudopterygium.

• Malignant

pterygium(rare):recurrent

pterygium with restriction of

ocular movements.

Symptoms

• Asymptomatic• Foreign body sensation• Discomfort• Congestion(redness)• Irritation and grittiness-interference with precorneal

tear film.• Interference with vision-obscuring visual axis -inducing astigmatism(WTR) • Cosmesis• Diplopia

Differential diagnosis

Pseudopterygium Most often hx of previous infective, chemical, thermal, or traumatic injury to the cornea.May occur at multiple locations and is not restricted to the 3 and 9 o'clock (interpalpebral) positions.

-Slit-lamp examination: reveals lesion to be adhesion of a fold of conjunctiva, which has occurred as a response to a previous peripheral corneal ulcer/inflammation.-Lesion typically only fixed at its apex to the cornea so that a probe may be passed underneath its body at the limbus, while a true pterygium adheres to the underlying cornea throughout its length. Thinning of the underlying cornea may be seen at its head.

Condition Signs and symptoms Tests

Pinguecula Does not encroach on the cornea.

Slit-lamp examination: reveals exact extent and nature of lesion. A pingueculum is limited to limbus and conjunctiva and does not encroach onto the cornea.

Marginal keratitis Associated with blepharitis. Infiltrate on corneal surface is separated by a clear zone from the limbus. Occur at 2, 4, 8, and 10 o'clock position. Does not have typical pterygium shape. Often superior and inferior.

Corneal swab/scraping: microscopy and culture positive for infecting organism, but infecting organisms are often not detected, as many cases are due to an inflammatory reaction to staphylococcal proteins

Corneal micropannus Hx of trachoma or lack of corneal oxygenation due to excessive contact lens wear.

Slit-lamp examination: reveals encroachment of fine blood vessels onto corneal surface.

Conjunctival carcinoma in situ/ bowens epithlioma.

Rare. Does not have typical pterygium shape. Not restricted to the 3 and 9 o'clock (interpalpebral) positions and can occur at any position on the cornea.

Slit-lamp examination: gelatinous-appearing mass.Biopsy: cytological features of a squamous cell carcinoma, but the basal membrane of the epithelium remains intact.

Squamous cell carcinoma

Rare. Does not have typical pterygium shape. Not restricted to the 3 and 9 o'clock (interpalpebral) positions and can occur at any position on the cornea. May arise from a pterygium, carcinoma in situ, or de novo.

Slit-lamp examination: surface may appear keratinised and friable.Biopsy: well-differentiated squamous cell carcinoma with invasion of the basal membrane.

Limbal dermoid Benign choriostomatous tissue. MC site:inferior temporal quadrant.

Histology contains abberant tissue like epidermal appendages,connective tissue,skin,fatmuscle teeth.

Treatment OptionsManaging the Menace

Historical aspects • Susruta,(before 1000 B.C.)

the Indian physician who was the world’s first surgeon-ophthalmologist described his operative procedure, in which he combined surgical removal with adjunctive chemical therapy

• 1953, Rosenthal reviewed surgical treatments and stated that pterygia have been “incised, removed, split, transplanted, excised, cauterized, grafted, inverted, galvanized, heated, dissected, rotated, coagulated, repositioned and irradiated.”

Treatment

• Medical Treatment– Symptomatic patients- Tear substitutes

– Inflammation- Topical steroids

– Sunglasses- to reduce UV exposure and decrease growth stimulus

Surgical management

Indications for Surgery1. Extension to the visual axis and induced

astigmatism.2. Recurrent irritation.3. Cosmetic- patient should be explained there is

fairly high risk of recurrence, which may be more unsightly.

A variety of pterygium operations illustrated in1950 (Archs Ophthal, 1950,Vol. 44)

• Modern pterygium surgery divided into four main category1. Bare sclera excision2. Excision with conjunctival closure/transposition3. Excision with antimitotic adjunctive therapies4. Ocular surface transplantation techniques

1.Bare sclera excission

• first described in 1948 by D’Ombrain• Principle- leaving a strip of bare sclera allowed the cornea,

time to heal• Recurrence rate range from 24% to 89%• Recurrence is highly aggressive • Symblepharon, restriction of motility and gaze dependent

diplopia may occur• Complication

– Scleral thinning– Irregular astigmatism– Dellen formation at sceral bed

2.Excision with ConjunctivalClosure/Transposition

• Bare sclera- does not comply with general principles of wound healing and closure

• Wound closure may be simple approximation of undermined conjunctival margins, with or without relaxing incisions

• may be effected by conjunctival transposition by a rotational pedicle flap from above or below

• Recurrence rates are similar

3.Excision with Adjunctive Medical Therapy

• Sushruta- introduced chemicals or chemical cautery• Radiation therapy- Terson in 1911(radium)• Estrada used X-rays • Iliff (1947)- employed beta irradiation with the means of a

radon applicator• Beta irradiation

– Strontium 90 source– total doses varying from 2000 rads to 6000 rads– Treatment periods - single immediate postoperative dose to

weekly doses for six weeks after surgery– Recurrence rate is around 10%

Beta Irradiation

• Complications– Milder reactions– sectoral cataract formation– iris atrophy, scleral necrosis – Melting– Limbal stem cell deficiency

• Use should be restricted to severe or repeated pterygium recurrences with a justifiable risk-benefit ratio

Mitomycin C

• Kunimoto and Mori (1963) reported success with post-operative MMC 0.04%

• inhibits DNA, RNA and protein synthesis• 0.01% twice a day for five days• Complications - Iritis, limbal avascularity, scleral melting or

calcific plaque formation, corneal decompensation, scleral or corneal perforations, secondary glaucoma and cataract

• surgeons now advocate a single intra-operative application of MMC 0.02%

• Recurrence rate 2.3%

Thiotepa

• Nitrogen mustard alkylating agent antimitotic property• Radiomimetic- obliterates vascular endothelial

cells.• Dose:1:2000 every 3 hours for 6 weeks.• Used in bare sclera method.• Complication: scleral thinning.• Recurrence:10-16%

5-fluorouracil

• Antiproliferative• Inhibits thymidylate synthetase, thus inhibits

DNA.• Only cells in the synthesis phase are affected,

allowing the remaining cells to continue to proliferate after exposure to 5-FU.

Cyclosporine A

• Immunosuppresant drug.• Dose: 0.05% topical for 3 months following

pterygium excision.

• Safe and effective.

• Low recurrence rate(3.4%)

Bevacizumab

• Inhibit neovascularisation.• Stop the progression or prevent the

recurrence.

• Case reported by Wu and co workers.Topical bevacizumab eye drops 25mg/ml 4times

for 3weeks.• No recurrence in 1year follow up period.

4. Ocular Surface Transplantation Techniques

• transplantation procedures currently performed are: 1. Conjunctival autograft transplantation2. Modifications of conjunctival autografting:

a. Conjunctival rotational autograftingb. Annular conjunctival autografting

3. Conjunctival limbal autograft4. Amniotic membrane transplantation

Conjunctival Autografting(CAU)

• Now recognized as procedure of choice for pterygium surgery in terms of the efficacy and safety

• Recurrence rate is 2%• 1977, Thoft first described the procedure of

conjunctival transplantation• 1931 Gomez-Marquez, utilized superior bulbar

conjunctiva from the contralateral eye• 1985 Keynon proposed the current conjunctival

autograft transplantation technique• low recurrence rate (2%)

Fibrin glue and conjunctival auto graft

• Mechanism of action: it acts forming a fibrin clot between graft and host tissue.

• Advantages : decreases the post op pain. reduces the surgical time as well as recurrence rate.Disadvantage : not FDA approved. graft dehiscence. infection, discomfort, costRecurrence rate: less as compared to suture.

CAU-Post operative care

• Avoid exposure to sunlight.

• Use of dark sun glasses.

• Topical steroid antibiotic drops, topical NSAIDS, artificial tears.

• Complete healing expected between 6-8weeks.

• Topical medications should be tapered. Lubricants should remain for 3months.

• Instruction to patient: avoid exposure to sunlight.

Complications

• Graft failure.• Granuloma formation.• Conjunctival infection.• Suture detachment.• Delayed healing.• Recurrence.

Conjuctival limbal autograft (CLAU)

• Principle- “corneal limbus as the source of limbal stem cells responsible for corneal epithelial cell maintenance”

• similar to conjunctival autografting• Except that the limbal edge of the donor graft is

extended to include limbal epithelium– superficial keratectomy– or by superficial lamellar dissection

• Recurrence rate is similar or higher as to CAU

Amniotic Membrane Transplantation

• As an alternative basement membrane substrate for use in ocular surface transplantation

• effective in reducing scarring and fibrosis• recently has also been shown to suppress TGF-β

signaling of fibroblasts• Advantages– Relatively easy– Good cosmetic result

• Disadvantage– less efficient than conjunctival autografting (Prabhasawat

reported a 13% recurrence rate)

Pterygium Recurrence• Growth of fibrovascular tissue across the limbus

onto cornea after initial removal.

• Excludes persistence of deeper corneal vessels and scarring which may remain even after adequate removal.

• Bunching of conjunctiva and formation of parallel loops of vessels, which aim almost like an arrowhead at the limbus, usually denotes a conjunctival recurrence.

Proposed Recurrence Grading System

• Grade 1 – normal appearing operative site.

• Grade 2 – fine episcleral vessels in the site extending to the limbus.

• Grade 3 – additional fibrous tissues in site.

• Grade 4 – actual corneal recurrence.

Excision of Recurrent Pterygia

• Why different??– subconjunctival fibrous tissue is more abundant and is tightly

bound to the underlying sclera– usually cannot be avulsed from the cornea and, therefore

must be dissected– Important to resect all fibrous tissue and any symblephara

• Treatment option– Superficial keratectomy– Deep lamellar keratectomy and inlay graft– Adjunctive therapy

Under trial

• ANECORTANE ACETATE:

Angiostatic steroid: Inhibits the blood vessels

Topical 1% have inhibitory effect on pterygium regrowth following recurrenr pterygium excision.

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