Pars Planitis

Pars Planitis is a disease of the eye that is characterized by inflammation of the narrowed area (pars plana) between the colored part of the eye (iris) and the choroid. This may lead to blurred vision; dark, floating spots in the vision; and progressive vision loss.

1. PARS PLANITIS Shah-Noor Hassan FCPS,FRCS(Glasgow) Vitreo -Retina Consultant Bangladesh Eye Hospital & Institute

2. Checklist History Epidemiology Etiology , pathogenesis Pathology , Clinical features Complications Clinical course Investigations Differentials Management Summary

3. History Cyclitis- Fuchs in 1908, Duke-Elder 1941 Peripheral uveitis- Schepens-1950 Peripheral cyclitis- Brockhurst et.al. - 1960 Pars planitis- Welch et.al. - 1960 Chronic cyclitis- Hogan & Kimura in 1961 Vitritis- Gass et.al. - 1968 Intermediate uveitis- IUSG- 1987 SUN working group-2004

4. Nomenclature Standardization of Uveitis Nomenclature working group classification Idiopathic form of intermediate uveitis Includes snowballs and snowbanking If associated with diseases like Sarcoidosis and Lyme disease then included in intermediate uveitis

5. Epidemiology 10-25 % of all the uveitis cases Children and young adults Can occur at any age Both sexes are equally affected 80% are bilateral Less in Chinese and Japanese population

6. Etiology Idiopathic No known hereditary or environmental factors Some isolated cases of familial pars planitis Associated with various systemic diseases Most common- multiple sclerosis, sarcoidosis

7. Pathogenesis Immune mediated response But the antigenic stimulus remains speculative Davis and colleagues Stage 1- immunologically mediated Stage 2- Non specific breakdown of intraocular regulatory mechanisms (Not necessarily an autoimmune mechanism but even exogenous viral or bacterial antigens may be responsible)

8. Pathogenesis Escape from regulatory control of Helper T cells directed against these antigens Defective intraocular T cell regulation of B cells Decreased helper to suppressor T cell ratios in aqueous and peripheral blood Other mechanisms Anterior chamber associated immune deviation Auto retinal antibodies Related to Demyelination HLA-DR15 and HLA-A28 positivity Nucleoporin like protien-nup36

9. Pathology Peripheral retina and ciliary body demonstrate condensed vitreous , fibroblasts, spindle cells, lymphocytes and blood vessels Prominent lymphocyte cuffing of retinal veins Pars plana exudates Loose fibrovascular layer containing scattered mononuclear inflammatory cells and a few fibrocyte like cells Fibroglial tissue consists of vitreous collagen, mullers cells and probable fibrous astrocytes

10. Clinical features Floaters and hazy vision No pain, photophobia, redness First episode is associated with a more severe and symptomatic iridocyclitis Subsequent episodes have a chronic course……. One eye symptomatic other eye may be asymptomatic and even show signs of active disease

11. Presentation VISION LOSS CME, ERM PSC Vitreous Opacification Membranes Retinal Detachment Vitreous Hemorrhage

12. Presentation Cells, flare, KPs in AC, synechiae (Spill over anterior segment inflammation) Snow balls (organized vitreous inflammatory cells ) Snow banking (exudates at pars plana) May be localised to inferior half

13. Presentation Peripheral vasculitis CME, Peripapillary retinal edema Vitritis, Cyclitis Vitreous hemorrhage Band shaped keratopathy

14. Effect on macula Macular edema (CME) and maculopathy (12-82 %) Most common cause of visual loss Incidence increases with duration and severity of disease

15. Vitreous involvement Vitritis Snowball formation Vitreous membranes and floaters Vitreous hemorrhage

16. Retinal involvement Retinal vascular changes Tortuosity of arterioles and venules Peripheral vascular sheathing (Periphlebitis-16-36 %) Neovascularizations (6.5%) Retinal detachment (2.2-51 %) Causes of RD Vitreous traction due to long standing inflammation and subsequent hole formation Exudative detachment secondary to uvietis inflammation

17. Optic nerve involvement Disc edema- 3-38% Optic neuritis with or without multiple sclerosis was seen in 7.4 %

18. Complications Glaucoma Acute uveitis- 7.6 % Chronic – 6.5% at one year, 11.1 at 5 years Causes of glaucoma Active inflammation Steroid usage Increasing age Number of years since diagnosis

19. Cataract 15-50% of eyes Posterior or anterior subcapsular At times posterior cortical even posterior polar have been reported Incidence increases with duration and severity of disease If treated earlier with immunosuppressive rather than corticosteroids cataract formation is less severe

20. Types Of Retinal Detachment Exudative RD in 5-17% Vitreoretinal traction - in 3-22% TRRD Brockhurst and Schepens – 4 types of RRD Type I: - Low lying, chronic, associated with demarcation lines Small breaks near ora with exudates Benign course

21. Types Of Retinal Detachment Type II: Large dialysis at the posterior edge of the pars plana exudate Slowly progressive May resolve spontaneously if VR exudation occludes the break Seen in pts with a mild chronic inflammatory course Type III: Rapidly progressive Large breaks associated with NVVB and circumferential pars plana exudates. Associated with severe chronic uveitis.

22. Types Of Retinal Detachment Type IV: Anterior PVR with vascular cicatricial tissue  circumferential traction Fixed folds extending from periphery to the disc and total RD Breaks are difficult to visualize B’coz extensive pars plana exudates Seen in rapidly progressive form of uveitis Extremely difficult to repair Poor functional and anatomic prognosis

23. Pars planitis in children More so as an intermediate uveitis JIA most common cause (30%) 1.8-29% of all uveitis Of which 25 % are pars planitis Mean age 8.5-10.9 years Male preponderence Bilateral 84-94 % Resolves over several years Severe visual loss is uncommon

24. STANDARDIZATION OF UVEITIS NOMENCLATURE

25. Diagnosis

26. Diagnosis: Clinical History Clinical findings Duration of symptoms, recurrences Fever , fatigue or night sweats are typical signs - Sarcoidosis & TB Loss of sensitivity or paresthesias of hands, arms or legs - Multiple sclerosis Dermatitis, Arthritis– Lyme Contact with cats – possibility of Bartonella infection

27. Ophthalmic investigations V/A SL biomicroscopy IOP and Fundus examination with scleral depression Amsler grid

28. OCT - Macular oedema Fluorescein Angiogram- Vasculitis ,CNP areas , New vessels & CME B scan (Hazy media) UBM Diagnostic vitrectomy Ophthalmic investigations

29. To rule out secondary causes… Complete hemogram ELISA for tuberculosis and toxoplasma CXR Galium Scan and Chest CT Lab Inv: - ACE levels- elevated in 60-90% of active sarcoid patients Lysozyme level - Elevated in granulomatous disorders viz sarcoid , TB, and leprosy Elevated antibody titre against Borrelia burgdorferi Sarcoidosis Tuberculosis.

30. Differential diagnosis Non infectious Multiple sclerosis (3-27 %) Sarcoidosis (23-26%, IU developing sarcoidosis- 2-10%) Intraocular lymphoma (PCNSL- 10-20% have vitreous inflam ) Infectious conditions Tuberculosis Syphilis (10.3%) Lyme disease Toxoplasma Toxocariasis HTLV-1, EBV, Cat scratch disease Endogenous endophthalmitis ARN, Eales , VKH, Fuch’s

31. MANAGEMENT

32. Four Step Approach (Kaplan et al)

33. Modified 5 step program: S.Foster et al Topical +/ Periocular corticosteroids Oral +/ Topical NSAID After 3rd injection Systemic C steroids Inflammation persists or recurs Peripheral retinal cryopexy /BIOL Recur following 6 th regional steroid injection PPV/ Immunosupression Recalcitrant inflammation

34. Addition of systemic steroid or immunosuppressive agents

35. Corticosteroids Drop in VA due to vitritis, CME, progression of neovascularization at the vitreous base Periocular steroids- Long acting Methyl prednisone (40 mg ) Triamcinolone acetonide (20 mg) Complications- Glaucoma Cataract Aponeurotic ptosis Enophthalmos Orbital scarring

36. Corticosteroids IVTA can be given in cases of severe macular edema Complications Cataract Glaucoma Endophthalmitis

37. Oral steroids Indicated if the disease activity is not controlled with periocular steroids Prednisolone 1 mg/kg/day tapered once response occurs

38. Immunosuppressive agents Antimetabolites : Methotrexate , Azathioprine Alkylating Agents : Cyclophosphamide , Chlorambucil Immunomodulators : Cyclosporine , Tacrolimus Complications GI upset Hepatotoxicity Bone marrow suppression

39. Methotrexate Folate analogue which inhibits dihydrofolate reductase 7.5-25 mg per week oral/subcutaneous Can also lead to pneumonitis Effective and safe for chronic anterior and IU in children

40. Azathioprine Purine nucleoside analogue Alters purine metabolism 50-150 mg per day GI upset and hepatotoxicity Mycophenolate mofetil Inhibits purine synthesis Prevents replication of T and B lymphocytes 1-3 mg per day Mycophenolate is faster amongst the 3 in controlling inflammation

41. Inhibitors of T-cell signaling Cyclosporine and Tacrolimus Inhibit NF-AT (Nuclear Factor of Activated T-cells ) Nephrotoxicity and hypertension are important complications Biological response modifiers Daclizumab Infliximab Eternacept Interferon alpha

42. Biological response modifiers Daclizumab Humanized monoclonal ant-IL-2 receptor alpha antibody Suppresses auto reactive T-cells 1 mg/kg IV every 2 weeks for 5 doses Increase risk of infection

43. Biological response modifiers Infliximab Binds to TNF and prevents its action on target tissues Eternacept Dimeric, fully human, soluble TNF receptor Binds tightly and specifically to circulating and cell-bound TNF Adalimumab Can be self administered as a subcutaneous injection Fully humanized so less chances of antibody formation Disseminated tuberculosis is one of the fatal complications

44. Newer steroid implants Retisert Fluocinolone acetonide implant Duration of 30 months Ozurdex Dexamethasone implant

45. Ablative procedures Failed drug therapy At times cryotherapy is preferred before immunosuppressive Rx Aim To treat neovascularization associated with the exudates To destroy the peripheral vessels which bring in the inflammatory mediators

46. Double row ,single freeze Apply to pars plana and posterior to it CONFLUENT BURNS Extend 1 clock hr on either side of all areas affected by inflammation EFFECTS Decreases vitritis and improves VA Decrease in fluorescein in the treated area Induce regression of this NVVB and consequently stabilize inflammation Cryo ablation

47. LASER ablation LASER photocoagulation works as effective as cryo 3-4 rows of burns are placed at the pars plana and peripheral retina Works on the same mechanism as cryo

48. Vitrectomy Vitrectomy for uveitis began in late 1970s Aims Get rid of inflammatory mediators and immunologically competent cells Clear the media Indications Refractory uveitis Vision loss due to densely opacified vitreous Scar tissue pulling on ciliary body causing hypotony CME, ERM Dense PCO TRD

49. MANAGEMENT OF CATARACT: Eye - quiet for 3 months Preoperative – Start steroids 3 days prior Postoperative - slow taper. Technique – As preferred by surgeon Minimal trauma Preferably heparin coated IOL

50. Other trails going on…. ……………none other than anti VEGF agents LUCENTIS is being evaluated in cases of uveitis with macular edema NO PRIZES FOR AN ACCURATE GUESS………!

51. What’s new…. Anti VEGF agents are being evaluated in cases of uveitis with macular edema Lucentis and Avastin have been proved to be effective in cases of uveitic CME

52. Nevanac in pars planitis Case 1: - Short term benefit in cases of recurrent intermediate uveitis

53. Case 2 Rapid resolution of vitritis in uncomplicated case of intermediate uveitis

54. Case 3 Fresh case of pars planitis with CME Nevanac improved the CME