|Year : 1993 | Volume
| Issue : 3 | Page : 133-141
Practical concepts in the management of uveitis
Medical Research Foundation, Madras, India
Medical Research Foundation, 18 College Road, Madras - 600 006
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Biswas J. Practical concepts in the management of uveitis. Indian J Ophthalmol 1993;41:133-41
Uveitis is often a vision-threatening intraocular inflammation. The management of uveitis should therefore be carefully and specifically planned for each patient and be instituted as soon as possible. The following steps represent a suggested approach to the management of a case of uveitis:
1. Elicit a uveitis-oriented history.
2. Make a clinical assessment of the disease which should include the following details:
a. Anatomic site of uveitis: anterior, intermediate (pars planitis), posterior (retinal, choroidal, or retinochoroidal) or panuveitis.
b. Stage (acute, chronic, recurrent, healed) and severity (mild, moderate, severe).
c. Vision: Reversible or nonreversible loss.
d. In a case of severe panuveitis, rule out endogenous and exogenous endophthalmitis (if uveitis occurs following surgery or trauma).
3. Make a short list of differential diagnosis and order 'tailored laboratory tests'.
4. Correlate clinical findings with laboratory results and ancillary tests, such as, Fluorescein angiography, to reach as precise a diagnosis as possible.
5. Institute appropriate treatment and monitor the drug.
Systematic and detailed ocular examination will often enable the ophthalmologist to arrive at a provisional diagnosis and to start early therapy which may need modification in accordance with the results of the investigations.
| I. GUIDELINES FOR THERAPY OF UVEITIS|| |
The strategy for treatment in uveitis can be divided into three parts :
A. Treatment of the specific causative agent.
B. Nonspecific treatment of intraocular inflammation.
C. Treatment of complications, such as cataract and glaucoma.
Besides that, a patient suffering from uveitis can have associated active systemic diseases, such as sarcoidosis, syphilis, and leprosy, which will also require appropriate specific treatment.
A. TREATMENT OF SPECIFIC CAUSATIVE AGENT
1. Ocular toxoplasmosis  Any of the two regimens given below can be followed.
a. Pyrimethamine - sulphadiazine - corticosteroid - folinic acid combination. Pyrimethamine (Daraprim) - 75 to 100 mg loading dose on the first day, followed by 25 mg/day for four to six weeks.
Sulphadiazine - 2 gm orally loading dose followed by 1 gm four times daily for four to six weeks. Corticosteroid - Prednisolone 40 to 60 mg/day from the third to seventh day which is then tapered gradually. It should be tapered off before antimicrobial therapy is discontinued. Folinic acid - 5 mg tablet two or three times weekly.
b. Clindamycin-sulphadiazine-corticosteroid combination.
Clindamycin (Dalacin C) - 300 mg four times daily for four to six weeks.
Sulphadiazine and corticosteroid - as mentioned in the previous regimen. Clindamycin can cause pseudomembranous colitis and should be discontinued if the patient develops diarrhoea.
Recently, there have been reports of successful treatment with cotrimoxazole or tetracycline sub in combination with systemic steroid. Depot steroid injection is contraindicated in ocular toxoplasmosis due to its permissive effect on organisms.
2. Ocular toxocariasis
a. Peripheral lesion : No treatment is advised.
b. Posterior pole lesion or endophthalmitis. Systemic corticosteroids 40 mg/day alone or in combination with an antihelminthic, such as, thiabendazole (20 mg/day for five to seven days) is used. Anti-microbial agents should not be used alone due to the possibility of severe intraocular inflammation caused by toxins liberated from the dead parasite. Vitrectomy may be required in recalcitrant cases of endophthalmitis.
3. Tubercular uveitis
The diagnosis of tubercular uveitis is often presumptive. There is no specific test for tubercular uveitis. A positive skin test with tuberculoprotein (Mantoux test) can be fallacious as a large percentage of normal persons are exposed to tubercle bacilli and show positive reaction. Tubercular uveitis must be suspected in any case of granulomatous anterior uveitis, solitary or multiple choroidal tubercles, choroiditis or panuveitis. For example, a patient with miliary tuberculosis can have choroidal infiltrate (miliary tubercle) in the active stage of the disease. Generally, most patients do not have coexistent active pulmonary or other extraocular tubercular infections. Abrams and Schlaegel  have suggested a three-week trial of isoniazid 300 mg/ day orally in suspected cases of tubercular uveitis. If this regimen led to improvement, they recommended a full course of anti-tubercular therapy. In some cases a systemic steroid can be given with anti-tubercular treatment to reduce intraocular inflammation.
The commonly used anti-tubercular regimens  are listed in [Table - 1].
B. NONSPECIFIC TREATMENT OF INTRAOCULAR INFLAMMATION
Modalities of treatment:
1. Medical treatment.
2. Laser photocoagulation and cryotherapy.
3. Surgical treatment.
1. Medical Treatment
The most common groups of drugs used in uveitis are given below:
a. Steroids - These can be given in various ways:
(i) Topical - drops or ointment
(ii) Periocular injections - subconjunctival,
c. Nonsteroidal anti-inflammatory agents.
d. Immunosuppressive agents.
(i) Topical Steroids - These are absorbed quite well through the cornea and form the mainstay of therapy in anterior uveitis. Topical steroids do not reach the posterior segment to the required extent and so have no beneficial effect in posterior uveitis. Common topical corticosteroid preparations are given in [Table - 2].
Suspensions have better penetration due to their biphasic nature. They need to be vigorously shaken before application. Topical drops can be applied as frequently as every one hour or as infrequently as once every alternate day. The frequency of usage basically depends upon the severity of the inflammation.
Ointments have been found to be less effective than drops. They should preferably be applied at bedtime as they are greasy and can blur vision.
Steroid-induced glaucoma This can occur in about 30 to 40% of the cases on prolonged usage (usually over six weeks). The intraocular pressure needs to be constantly monitored in patients on prolonged topical steroid therapy. It is advisable to taper off the drops and to restart them on recurrence of the uveitis rather than use them indefinitely. Weaker steroids, for example, medrysone or fluorometholone are less likely to cause a rise in the intraocular pressure and can be used in maintenance therapy instead.
Posterior subcapsular cataract It occurs more commonly after systemic steroid therapy. However, prolonged use of a topical steroid can also cause posterior subcapsular cataract.
Predisposition to bacterial and fungal infection.
Reactivation and recurrence of Herpes simplex infection.
(ii) Periocular Injection
With this modality of treatment maximum concentration in uveal tissue is achieved with minimal systemic side effects. An experimental study has shown that both methyl prednisolone and triamcinolone acetonide penetrate well into the vitreous cavity and retina following posterior sub-Tenon's injection.  The effect of short-acting depot steroids lasts for a few hours to one day while the effect of long-acting depot steroids lasts for two to three weeks. A list of the commonly used injectable corticosteroid preparations is given in [Table - 3].
The periocular injections can be given by any of the following route, namely subconjunctival, posterior sub-Tenon's and retrobulbar.
It is useful in cases of anterior uveitis which do not respond to topical therapy. Subconjunctival injections are, however, ineffective in posterior uveitis as intraocular penetration is poor.
Technique: After topical anaesthesia, the conjunctiva and Tenon's capsule are lifted with a toothed forceps. The patient is asked to look away from the site of injection. A maximum of 0.5 ml of the drug is injected with a 3/8 inch, 25 or 27 gauge disposable needle.
Posterior sub-Tenon's injections 
Posterior sub-Tenon's injection is recommended in intermediate uveitis and in posterior uveitis along with systemic steroids and in panuveitis along with systemic and topical steroids.
Technique: The best site for injection is the upper temporal quadrant. The upper eyelid is elevated and the patient is instructed to look down and in. One millilitre of the drug is taken in a 2 ml syringe with a 27 gauge, 5/8 inch disposable needle. With the bevel towards the globe, the needle is introduced into the superior bulbar conjunctiva and moved from side to side and injected into the posterior sub-Tenon's space [Figure - 1].
This is seldom preferred because of the high degree of risk involved in the technique and the poor intraocular penetration of the drug. Complications related to the periocular injection procedure include:
Inadvertent injection into the globe
Optic nerve injury
Complications related to the effect of depot preparation of periocular corticosteroids include:
Increased intraocular pressure
Scarring between conjunctiva and globe
Posterior subcapsular cataract
Hypersensitivity tissue reaction
Subdermal fat atrophy
Ptosis and extraocular muscle paresis
Potentiation of infection
Worsening of infectious uveitis
(iii) Systemic Steroids
Systemic steroid therapy is used predominantly in posterior segment involvement. It is also used in cases of anterior or intermediate uveitis which have not responded to topical therapy.
The common steroid preparations are listed in [Table - 4].
Oral corticosteroids have several potential hazards. A definite plan of therapy must be made before their use.
General guidelines for oral corticosteroid therapy are given below: (Modified from Gordon DM )
Use enough, soon enough, often enough and long enough to secure the desired results.
Start with a high dose and taper according to the clinical response. An oral steroid is started with the maximum dosage (1 mg/kg of body weight) and when the desired effect is achieved, is given every alternate day.
If therapy prolongs for over two weeks, never stop abruptly at a high dosage. Taper it slowly. If therapy is to be discontinued, an attempt should be made to control the disease with periocular injection.
Suppress inflammation till the pathogenic effect ends. Determine the minimal maintenance dose by a process of trial and error. Make an effort to reduce the dosage if there is no sign of relapse. Increase the dosage immediately in case of recurrence.
The dosage of steroid should not be tapered with a predetermined plan but in accordance to the response of the disease.
Aseptic necrosis of head of femur
Reactivation of infections
Increase in the severity of pre-existing disease such as diabetes, hypertension.
Limitation of growth in children
Pregnancy • Peptic ulcer
Osteoporosis especially • Active infection
Diabetes mellitus • Cardiovascular
These are given as a supportive measure. They cause paresis of iris and ciliary muscles and keep the pupil mobile thereby preventing the formation of synechiae. A short-acting mydriatic/cycloplegic preparation is usually preferred to long-acting cycloplegics, for example, atropine which can cause synechiae formation in the dilated position. A list of mydriatic/ cycloplegic drugs is given in [Table - 5].
c. NonSteroidal Anti-Inflammatory Drugs
These include inhibitors of arachidonic acid metabolism such as indomethacin, flurbiprofen and diclofenac sodium. Fluribiprofen, diclofenac sodium and indomethacin are now available in topical formulation. However, their efficacy in treating acute intraocular inflammation is doubtful. The commonly Systemic nonsteroidal anti-inflammatory agents, such as flurbiprofen, diclofenac sodium, indomethacin, and ibuprofen have no proven value in uveitis.
d. Immunosuppressive Agents
Immunosuppressive agents are now the first choice of therapy for corticosteroid-resistant cases of uveitis and in cases where corticosteroids are contraindicated.
The side effects and potential complications of these agents are many and at times fatal. These are therefore reserved as the second line of treatment in many cases, the first being corticosteroids.
An immunosuppressive agent should be used with caution. A generalised guideline for the use of immunosuppressive drugs is given below.
Immunosuppressive agents are used only when:
Uveitis is vision-threatening.
Reversibility of the disease process is possible.
An objective evaluation of the process of disease is possible.
No response to an adequate regimen of corticosteroids is found.
Systemic corticosteroids are contraindicated.
Active infection is absent.
Haematologic contraindication is absent.
The patient understands the need for a periodic follow-up by the ophthalmologist and the internist.
Informed consent is obtained.
In 1980, the International Uveitis Study Group (IUSG)  recommended a guideline for the use of immunosuppressive agents which is given in [Table - 7].
The common immunosuppressive agents, their earliest clinical response and side effects sub are given in [Table - 8].
2. Laser Photocoagulation and Cryotherapy
In some cases of ocular toxoplasmosis and ocular toxocariasis, laser photocoagulation has been tried. However, its use is limited as there is a potential risk of aggravating inflammation. Subretinal neovascularisation in presumed ocular histoplasmosis or in any other retinal/choroidal inflammation, if found approaching the fovea can be treated with laser photocoagulation. Cryotherapy  to vitreous base is found to be useful in cases of pars planitis refractory to periocular and systemic steroids.
3. Surgical Treatment
Therapeutic vitrectomy is recommended in cases of unresolving vitreous opacities following a complete course of medical therapy (corticosteroids and immunosuppressives). Vitrectomy has been found to be beneficial in recalcitrant pars planitis.  Recently there have been reports of successful removal of the subretinal neovascular membrane following a presumed ocular histoplasmosis with subsequent improvement of vision.  Retinal or retinochoroidal biopsy is indicated in some recalcitrant posterior uveitis and suspected reticulum cell sarcoma.
C. TREATMENT OF COMPLICATIONS
These include treatment of complicated -cataract, glaucoma, band keratopathy, and other corneal complications. Management of cataract extraction with or without intraocular lens implantation is discussed here.
1. Cataract extraction in patients with uveitis
Cataract extraction in a uveitis patient involves several associated risks and therefore requires special precautions. Guidelines for cataract extraction in a uveitis patient are given below:
a. The eye should be quiet for at least three months and preferably six months prior to cataract surgery.
b. Preoperative systemic steroid therapy 40 to 60 mg; day should be initiated three to four days prior to surgery.
c. Preoperative posterior sub-Tenon's injection of depot steroid (Triamcinolone acetonide or methyl prednisolone) should be, given three to four days prior to surgery.
d. Excessive manipulation of the iris during surgery should be avoided.
e. Extracapsular cataract extraction with meticulous clearing of all cortical materials is mandatory. Intracapsular cataract extraction is not preferred as inflammation could spread to the posterior segment.
f. Pupillary mobility is to be carefully maintained during the postoperative period by frequent use of short-acting mydriatic-cycloplegics.
g. Close monitoring of postoperative intraocular pressure is required.
h. Postoperative systemic corticosteroids are needed in case of excessive postoperative inflammation.
i. Lensectomy with pars plana vitrectomy is recommended in cataract patients with juvenile rheumatoid arthritis, pars planitis with unresolved vitreous opacities, and lens-induced uveitis.
2. Intraocular lens implantation in uveitis cases
Intraocular lens implantation in uveitis cases is still controversial.  Several reports with good results have been obtained in Fuch's heterochromic iridocyclitis, nongranulomatous anterior uveitis and in few cases of pars planitis.  The above guidelines for cataract extraction should be followed in intraocular lens implantation in uveitis cases. Posterior chamber intraocular lens implantation in the capsular bag is recommended.
| II. GUIDELINES FOR THERAPY OF INDIVIDUAL UVEITIC ENTITIES|| |
Specific treatment regimens for common uveitic entities are given below.
A. ANTERIOR UVEITIS
Most cases are found to be idiopathic and are treated nonspecifically. Treatment is monitored according to the stage and the severity as given below.
1. Severe: a. Topical steroid every hour
b. Short-acting mydriatic/ cycloplegic agent every 3 to 4 hours
2. Mild to a. Topical steroid
moderate: every 3 to 6 hours
b. short-acting mydriatic/ cycloplegic agent every 6 to. 8 hours
3. Chronic, Topical steroid can be used once
Low grade: daily or once on every alternate day. In case of uveitis associated with juvenile rheumatoid
arthritis, mydriatic alone may be used in the chronic phase.
General guidelines to the therapy are given in the flowchart [Figure - 2].
B. INTERMEDIATE UVEITIS (Pars planitis)
This disease is, by nature, slowly progressive and often self- limiting. Treatment is reserved for when the patient's vision is diminished to 6/12 or less, or there is evidence of cystoid macular oedema. A four-step approach by Kaplan sub as given below can be adopted.
Four-step treatment approach in pars planitis (According to Kaplan HJ )
Step 1: Posterior sub-Tenon injection of depot steroids (for example, methyl prednisolone or triamcinolone) is given. This can be repeated every three weeks. Two to three such injections at intervals of three weeks to one month often lead to resolution of an active pars planitis. If the patient has active and severe bilateral pars planitis, systemic corticosteroids 60 to 80 mg/day can also be given.
Step 2: If step 1 fails, cryotherapy to vitreous base is advised.
Step 3: If step 2 fails, pars plana vitrectomy can be done.
Step 4: If step 3 fails, immunosuppressive agents can be used.
General guidelines to therapy are given in the flowchart [Figure 3].
C. POSTERIOR UVEITIS
Posterior uveitis can be divided into the following two groups for therapeutic approach: 1. Due to specific infective aetiology.
Ocular toxoplasmosis, ocular toxocariasis, which have been discussed earlier in this article.
2. Idiopathic posterior uveitis.
Systemic steroids are indicated in visionthreatening idiopathic posterior uveitis. Mild posterior uveitis can be treated with posterior sub-Tenon injection of depot steroid alone.
General guidelines to the therapy are given in the flowchart [Figure - 4].
Guidelines for therapy of a few specific panuveitic entities are given below:
1. Sympathetic Ophthalmia and Vogt-Koyanagi
Harada's Disease 
In these two diseases systemic steroid is given in relatively higher dosage, for example, 80 to 200 mg based on the severity of inflammation. Systemic steroids in such cases are tapered relatively slowly and may require prolonged therapy, i.e. six months or more. In those patients who are unresponsive (after at least two weeks of maximum dose therapy) or intolerant to systemic steroid, immunosuppressive agents or cyclosporine can be used.
Controversy exists in the literature with regard to early enucleation of the injured eye in sympathetic ophthalmia. If the injured eye has the potential to recover vision, it is advisable to treat it medically as a case of bilateral panuveitis.
2. Behcet's Disease
Although systemic steroids have been found to be beneficial in the initial stage of the disease, they do not have much long-term benefit. Immunosuppressive agents such as, cholorambucil (6 to 12 mg/day), azathioprine (2.5 mg/kg/day) or cyclosporine (5 to 10 mg/kg of body weight day) have been found to be beneficial.
General guidelines to the therapy of panuveitis are given in the flowchart [Figure - 5].
| III. TREATMENT OF NEWER UVEITIC ENTITIES|| |
A. Acute retinal necrosis 
This is a rare and relatively new form of viral retinitis caused by the Herpes group of viruses. It occurs in a healthy individual and is characterised by unilateral or bilateral necrotising retinitis with confluent lesions starting from the peripheral retina and progressing concentrically towards the posterior pole.
Acyclovir (Zovirax) - 1500 mg/m 2/day intravenously for five to ten days followed by oral treatment at a dosage of 400 to 600 mg five times a day for up to six weeks is recommended. Oral prednisolone is given along with it in the dosage of 60 to 80 mg/day for one week followed by a tapering dose over six weeks.
B. Cytomegalovirus retinitis 
This is seen increasingly these days as an opportunistic viral infection in AIDS and following organ transplantation. The treatment regimen is given in [Table - 9].
C. Lyme diseases 
Several forms of uveitis (anterior, intermediate, panuveitis and choroiditis) have been reported in this newly recognised tick-borne infection caused by Borrelia burgdorferi.
Drug regimen for lyme borreliosis
Stage 1 and 2
Doxycycline 100 mg twice daily, orally
Amoxycillin 250 mg three times daily, orally
Erythromycin 250 mg four times daily, orally
Ceftriaxone 2 gm (intravenous) daily for 14 days. Penicillin G 10-20 million units (intravenous) daily.
| IV. NEW DRUGS IN UVEITIS|| |
FK.506: It is a new immunosuppressive agent which has been isolated in Japan from the fermentation broth of Streptomyces tsukubaenesis. This agent has immunologic properties similar to cyclosporine. The drug was found to be effective in cases of uveitis refractory to corticosteroids or immunosuppressive agents including cyclosporine.
The drug is given orally at a dosage of 0.15 to 0.2 mg/kg of body weight/day. 
Several drugs such as rapamycin, lefluonomide, and topical cyclosporin A have been reported to be beneficial in the treatment of experimental uveitis. However, their efficacy in clinical practice is yet to be established.
In conclusion,the strategy of treatment and the side effects of drugs should be discussed in detail with the patient and the family especially when systemic steroids and immunosuppressives are used which have serious side effects and are at times fatal.
| References|| |
Biswas J, and Rao NA. Management of intraocular inflammation: in Ryan SJ (ed), Retina. Vol 2. St. Louis: CV Mosby, 139-146, 1989.
Engstrom RE, Holland GN, Nussenblatt RB and Jabs DA Current practices in the management of ocular toxoplasmosis. Am J Ophthalmol. 111: 601-610, 1991.
Friedman E, and Friberg T Tetracycline in the treatment of toxoplasmic retinochoroiditis. Invest Ophthalmol Vis Sci (Suppl) 34:1106, 1993.
Abrams JA and Schlaegel TF. The role of isoniazid therapeutic test in tuberculous uveitis. Am J Ophthalmol. 94: 511-515, 1982.
Schneiderman TE, Munguia D, Polansky JR, Fauss DJ, Listhaus AD and Freeman WR. Intraocular corticosteroid penetration after periocular injection in humans and rabbits. Invest Ophthalmol Vis Sci (suppl). 33: 728, 1992.
Palestine AG. Medical therapy of uveitis. Focal points, Clinical module for the ophthalmologists. Vol VII. Module 8 American Academy of Ophthalmology. 111: 601, 1989.
Gordon DM. Diseases of the uveal tract. In Gordon, DM, ed: Medical management of ocular disease, New York, Harper & Row, Publishers Inc, 1964.
Hemady R, Tauber J, and Foster CS Immunosuppressive drugs in immune and inflammatory ocular disease. Surv Ophthalmol. 35: 369-385, 1991.
Kaplan HJ. Intermediate uveitis (pars planitis, chronic cyclitis)- a four-step approach to treatment. In Saari KM (ed): Uveitis Update. Amsterdam, Excerpta Medica, pp.169-172, 1984.
Goto H, and Rao NA. Sympathetic ophthalmia and Vogt-Koyanagi-Harada syndrome. Int Ophthalmol Clin. 30: 279-285, 1990.
Duker JS, and Blumenkranz MS. Diagnosis and management of the acute retinal necrosis (ARN) syndrome. Surv Ophthalmol. 35: 327-343, 1991.
Yoser SL, Forster DJ, and Rao NA. Systemic viral infections and their retinal and choroidal manifestations. Surv Ophthalmol. 37: 313-352, 1993.
Winward KE, Smith JL, Culbertson WW et
al. Ocular Lyme borreliosis. Am J Ophthalmol 108: 651-657, 1989.
Gharte KN, and Brockhurst RJ. Photocoagulation of active toxoplasmic retinochoroiditis. Am J Ophthalmol. 89: 858-864, 1980.
Aaberg TM, Cesarz TJ, and Flickinger RR. Treatment of peripheral uveoretinitis by cryotherapy. Am J Ophthalmol. 75: 685-688, 1973.
Mieler WF, Will BR, Lewis H, and Aaberg TM. Vitrectomy in the management of uveitis.Ophthalmology. 95(7): 859-864, 1988.
Thomas MA, and Kaplan HJ. Surgical removal of subfoveal neovascu1"- zation in presumed ocular histoplasmosis syndrome. Am J Ophthalmol. 111: 1-7, 1991.
Hooper PL, Rao NA, and Smith RE. Cataract extraction in uveitis patients. Surv Opthalmol. 35: 120-144, 1990
Foster CS, Fong LP, and Singh G. Cataract surgery and intraocular lens implantation in patients with uveitis. Ophthalmology. 96: 281-287, 1989.
Mochizuki M, Ikeda E, Shirao M. et al. Preclinical and clinical study of FK 506 uveitis. Curr Eye Res 11 (suppl): 87-95, 1992.
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6], [Table - 7], [Table - 8], [Table - 9]