All Posts tagged Cyclosporin

Cyclosporin Eye Drops: A magical steroid-sparing drug

Cyclosporin Eye Drops: A magical steroid-sparing drug

Cyclosporin Eyedrops are an effective therapeutic agent in the management of a variety of autoimmune diseases especially ocular surface disorders like vernal keratoconjunctivitis, dry eye syndrome, mild to moderate anterior scleritis, VKC, Mooren’s Ulcer, Neurotrophic Corneal Ulcer, Corneal Melting.

Mechanism of action: Cyclosporin is a new class of drug that appears to work by inhibiting cytokine production by immune cells (T lymphocytes) and interfering with the action of interleukin-2 (as in scleritis, Mooren’s ulcer, Dry eye syndrome). IgE mediated immediate hypersensitivity response as in VKC. Studies support the efficacy of topical cyclosporine treatment through its immunomodulatory action, reversing inflammation of the ocular surface and lacrimal glands.

Animal studies have shown that Cyclosporin has no intraocular penetration; it concentrates on the ocular surface which enhances its anti-inflammatory effect after long term use. Even after a year of regular topical therapy, none to minimal blood concentration is found in rabbits.

Rationale of using varying concentration of eyedrops: Cyclosporin eyedrops can be prepared in varying concentrations depending upon the severity of the ocular surface disease; if the inflammation is marked, then 1-2% concentration should be used, 3-4 times /day; gradually the strength and frequency is reduced according to the clinical improvement.

Preparation of eyedrops: Cyclosporin capsules are available in 25mg and 100 mg strength (Sandimum neural: Novartis) which contain a water miscible gel.

  • To make 1% concentration, take gel out of two 25 mg capsules by a disposable syringe, put it in a sterile eye drops bottle and add 5 ml distilled water. Shake it well and dispense.
  • For 2% concentration, take either one 100 mg capsule or four 25 mg capsules and mix their gel in 5 ml
  • For 0.5% concentration, take one 25 mg capsule + 5 ml distilled water.
  • For 0.05% concentration, take one 25 mg capsule + 10 ml distilled water.

Indications:

  • Mooren’s ulcer, Severe VKC, severe scleritis, corneal melt: 2%
  • Moderate Scleritis, moderate VKC, Stevens Johnson’s syndrome: 1%
  • Dry eyes: 0.5 – 0.05%

 

 

 

 

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A STEPWISE APPROACH TO DRY EYE

A STEPWISE APPROACH TO DRY EYE

Concept of A LACRIMAL FUNCTIONAL UNIT (LFU) 

It comprises of the lacrimal gland, Ocular Surface and a Neural Network to provide a feedback from ocular surface to the lacrimal gland. Only that amount of tears are produced as are required by the ocular surface, depending upon the information sent to the lacrimal gland through the neural network.

Pathogenesis of dry eye: A multifactorial disease. Either it results from reduced tear production with increased tear osmolarity & an inflamed ocular surface. Or increased tear evaporation due to deficiency of lipid layer. Or poor wetting of ocular surface causing dry, damaged corneal epithelium. Even in presence of adequate tear production.

Lipid layer deficiency: due to meibomian gland dysfunction  →  Tear evaporation.

Aqueous layer deficiency: in KCS which is divided into: SS (Sjogren’s Syndrome) as in RA, SLE, Multiple sclerosis and Non-SS KCS: in pregnancy, postmenopausal women, HRT

Mucin deficiency: Stevens Johnson syndrome, chemical burn, Trachoma, Ocular cicatricialPemphigoid  →     Poor Wetting of Ocular Surface.

 Predisposing Factors for Dry eye:

Old age: usually seen in post-menopausal women.

Connective tissue disorders

LASIK : lifting of corneal flap damages corneal nerves.

Drugs: beta blockers. antihistamines, AGT.

Diabetes: Type 2, impaired autonomic innervation to lacrimal gland, reduced corneal sensitivity, poor lac. Gland microvasculature, advanced glycation products activated cytokines.

Vitamin A deficiency

 Effects of Ageing:

Ageing causes androgen deficiency. Estrogen & androgen receptors are present in the lacrimal & meibomian glands. Androgens are trophic for lacrimal & meibomian glands. They are potent anti-inflammatoryagents  ( TGF beta) & suppress lymphocytic infiltration of lacimal glands. Androgen def. causes inflamed lacrimal and meibomian glands, with tear def. & hyperosmolar tears. These cause a pro-inflammatory environment on ocular surface. Also cytokine production and T-cell activation further inflame ocular surface, disrupt the neural arc.

Cytokines inhibit neuronal function. They convert androgens to estrogens and increase the level of tissue degrading enzymes

 MANAGEMENT OF DRY EYE

It is a STEP-WISE APPROACH. It is important to listen to patient’s symptoms, find and eliminate the predisposing factors and find and treat the cause. Simply prescribing artificial tears does not work. This is an ocular surface disease; unless a wetting surface is restored, loading the eye with tear drops is useless.

Smptoms: Burning, Blurring of vision,Photophobia,paradoxical tearing.All symptoms are worsened by smoking, reading, computer work. Find the predisposing factors by a careful history.

Examination: aim is to find the cause resulting in a dry eye and to grade its severity. Grading  decides the step-wise management and helps in assessing improvment on follow-up.

Grading of Dry Eye: according to symptoms & signs

 MANAGEMENTimage2

LEVEL 1:                                                                                                                LEVEL 2:

1: Environmental & dietary modification               Pt. symptoms don’t improve, T BUT &Schirmer =/< 10

2: Eliminate the cause.                                                   Add: Anti-inflammatory therapy:

3: Artificial tears.                                                                steroids, CsA, omega 3 fatty acids, Tetracyclines

4: Eyelid therapy.                                                             Punctal plugs

 Tetracyclines: antibacterial, anti-inflammatory, antiangiogenic, reduce lipase production→ FFA→stabilize tear film.

CyclosporinA : increases aqueous &meibomian sec., increases goblet cell count, decreases cytokines & inflammatory cells in conj.

 LEVEL 3:                                                                                                                                LEVEL 4:

If symptoms are severe, conj. & central corneal staining;              Severe symptoms, SPK+++, conj

TBUT & Schirmer< 5mm                                                                              Scarring/symblepharon, TBUT

 Permanent punctal occlusion                                                                 immediate, schirmer<2mm :

 Autologous serum                                                                                  Systemic immunosuppressant drugs.

 Soft contact lens                                                                                     Surgery: amniotic or mucus membrane graft, lid surgery, tarsorrhaphy

Autologous Serum: Contains trophic factors which promotes growth & migration of epi. cells. immunoglobulins, vitamins & are non-antigenic. Containdications; HIV, Hepatitis B, anaemia. Complications: bacterial keratitis, conjunctivitis, scleral vasculitis & melting.

FOLLOW-UP

1)      Note subjective improvement.

2)      Check the status of lid margins, cornea, tear meniscus.

3)      Perform Schirmer’s test & TFBUT every visit to gauge efficacy of therapy.

4)      NOTE: 3 layers of tear film; 3 tests to diagnose the abnormality of tear film.

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