An Ayurvedic Approach to Granulomatous Uveitis– A Case Study

Introduction

        Granulomatous uveitis refers to inflammation of the uveal tract, characterized by the formation of granulomas due to infectious or non-infectious causes. It may involve the iris, ciliary body, and choroid, and can be classified into anterior, intermediate, posterior, or panuveitis based on the anatomical site of inflammation. Granulomatous uveitis is further categorized by its etiology into infectious (e.g., tuberculosis, syphilis) or non-infectious (e.g., sarcoidosis, Vogt-Koyanagi-Harada disease) causes. Histologically, it is characterized by a granulomatous response that often includes multinucleated giant cells and epithelioid cells. Granulomatous uveitis may be associated with systemic diseases and, in some cases, may be the first manifestation of a serious underlying condition.

            The underlying pathophysiology involves an immune response to a specific antigen, leading to granuloma formation. In infections like tuberculosis, the antigen is typically microbial, whereas in non-infectious conditions like sarcoidosis, the exact antigen remains unidentified. The activation of T-helper cells, macrophages, and the release of pro-inflammatory cytokines like TNF-α and IFN-γ contribute to granuloma formation. Granulomatous uveitis can affect various parts of the eye, with posterior uveitis potentially causing permanent vision impairment.

              The middle layer of the eye, also known as the uvea (uva or “grape” in Greek), is made up of the iris, the ciliary body, and the choroid. Uveitis is an inflammation of the middle layer of the eye which can involve one, two, or all three parts of the uveal tract. It can be classified in several ways; anatomically into anterior, intermediate, posterior, or panuveitis according to the site of inflammation, etiologically into infectious or non-infectious uveitis according to the underlying cause, and histopathological into granulomatous or non-granulomatous uveitis according to the immunological response of the body to the cause of uveitis.[1]

            The exact pathophysiology of granulomatous uveitis depends on the underlying cause. However, a similar general mechanism is responsible for forming granulomas in most granulomatous inflammations regardless of the causative antigen. Tissue-resident antigen-presenting cells, such as dendritic cells and monocytes circulating in the blood, are responsible for first detecting an antigen, which is then presented to T helper cells, which in turn results in recruitment and activation of more circulating monocytes and lymphocytes into the affected tissue, with the production of various cytokines and chemokines including tumor necrosis factor-alpha and interferon-gamma that are responsible for regulating granulomatous immune responses, and the formation of epithelioid and multinucleated giant cells by the activated macrophages. These cells assemble around the culprit antigen, leading to granuloma formation.[2][3][4]

             This antigen may be of bacterial origin as in tuberculosis or of unknown origin as in sarcoidosis. [5] In lymphoma cases, inflammation may be due to a host immune response to lymphomatous cells or a paraneoplastic granulomatous inflammation. In contrast, in Vogt-Koyanagi-Harada disease and sympathetic ophthalmia, the altered immune response may be directed towards melanocytes. [6]

             Impairment in the immunosuppressive role of regulatory T cells may also contribute to the exaggerated immune response in granulomatous uveitis. Simultaneously, specific HLA class II antigens may play a role in the development of granulomatous inflammation. Blau syndrome is a monogenic familial autoinflammatory systemic granulomatous disease associated with a mutation in the NOD2 gene. This gene encodes a protein that is a member of the pattern-recognition intracellular receptor family, expressed in macrophages, monocytes, and dendritic cells, and plays an important role in the innate immune defense system against pathogens.[7,8]

     The mutation leads to the unfolding of the NOD2 protein from its autoinhibited state, leading to the hyperactivation of nuclear factor kappa B and the excessive production of inflammatory cytokines and chemokines, which results in systemic granulomatous inflammation, including skin rash, arthritis, and granulomatous uveitis. [9]

                      Patients with uveitis usually present with the blurring of vision, ocular pain, redness, and photophobia. These may vary according to the anatomical location of the inflammation. Anterior segment examination of a patient with granulomatous uveitis may reveal ciliary injection, elevated or decreased intraocular pressure, mutton fat keratic precipitates (large deposits on the back of the cornea), anterior chamber flare and cells, iris, and angle granulomas, anterior and posterior synechia, cataract especially posterior subcapsular, cataract surgery in phakoanaphylactic uveitis and anterior vitreous cells.

               Posterior segment examination may show vitritis, vitreous opacities, snowballs, snow banking in intermediate uveitis, perivascular exudates, retinal hemorrhages in retinal vasculitis, cystoid macular edema, and optic disc edema, as well as posterior segment complications such as choroidal neovascularization, retinal neovascularization, and epiretinal membrane.[10]

            Inflammation of uveal tissue from iris to pars plicata of ciliary body is called anterior  uveitis, inflammation  of  pars  plana  and  peripheral  part  of retina  and  underlying  choroid  is  called  intermediated uveitis and inflammation of choroid is called posterior uveitis. [11]

In posterior uveitis along with choroid it may also affect the retina and/or the optic nerve and may lead  to permanent  loss of  vision. It is one of the rare forms of uveitis  among all  other  types. It  is  a painless   condition   usually   characterized   by   visual symptoms  like defective  vision,  photopsia,  floaters, metamorphopsia and positive scotoma. This condition affects males and females in equal number and it appears most often to occur between ages of  20  and 50 years. The management of granulomatous uveitis is challenging. It includes treatments based on underlying cause ,anti inflammatory treatments , surgical interventions, antimicrobial or anti tubercular management should be adopted if the cause is infectious ,while Corticosteroids and  immune suppressor which tailored to specific auto immune conditions are administered if the cause is inflammatory. vitrectomy may be considered in the case of severe complications like macular edema, vitreous opacities.

                Effective management of granulomatous uveitis is multifactorial, requiring a comprehensive approach by addressing the underlying cause and preventing vision loss. This often includes antimicrobial treatment, immunosuppressive therapy, and surgical interventions when necessary. Challenges in management includes accurate diagnosis, monitoring treatment responses, managing side effects, handling disease recurrence, and preserving vision. The symptoms of granulomatous uveitis can be correlated with the Ayurvedic concept of Sashopha Akshipaka(~panopthalmitis). [12] Ayurvedic treatment approaches have been explored for managing this condition with improvement in visual acuity to 6/12 in the left eye and counting finger 2 .5 mt with a pinhole correction of 6/36 in the right eye. Slit-lamp examination revealed pigmentary deposits in both eyes, with posterior capsular opacification (PCO) in the right eye. Fundus examination showed bilateral macular edema and signs of peri-papillary atrophy.

Patient Information:

             A 29-year-old female patient presented to the Shalakya Tantra OPD at NIA Jaipur with a four-year history of bilateral non-infective granulomatous posterior uveitis with vitritis. She also reported a two-year history of persistent headaches. Initially, the patient was managed with oral and topical corticosteroids, which provided temporary symptomatic relief. However, her symptoms recurred after the steroids were withdrawn during pregnancy and again following cataract surgery.

                 The patient was apparently asymptomatic until four years ago, after which she gradually developed bilateral diminution of both distant and near vision, along with redness, watering, and photophobia. During this period, she received posterior sub-tenon injections of Tricort 40 mg in both eyes, which again provided only transient relief. Despite continued use of steroids, within three months her symptoms worsened, now accompanied by severe eyelid oedema.

                Steroids were discontinued temporarily due to her pregnancy and were later reintroduced postpartum. Within the span of one year post-delivery, the patient developed bilateral cataracts, for which she underwent surgical intervention, spaced one year apart between each eye.

In addition to ocular complaints, the patient had a history of multiple joint pains and was prescribed methotrexate, which initially provided relief for over a year. However, she began experiencing side effects such as persistent headaches, lethargy, and weight gain. As a result, methotrexate was discontinued in March 2024.

          There was no history suggestive of tuberculosis, hypertension, or diabetes mellitus.

Treatment Timeline Summary:

• Four years ago: Onset of ocular symptoms.
• First year: Steroid therapy initiated, including posterior sub-tenon Tricort injections.
• Pregnancy period: Temporary withdrawal of steroids.
• Post-delivery: Symptoms recurred, steroids resumed; developed bilateral cataracts.
• Within a year post-delivery: Cataract surgeries performed one year apart for each eye.
• Concurrent systemic symptoms: Methotrexate used for >1 year, discontinued in March 2024 due to adverse effects.
• As the patient had been on prolonged steroid therapy and methotrexate, any integrative Ayurvedic intervention must account for potential drug interactions, cumulative immunosuppression, and the patient’s recent systemic vulnerability. Close monitoring is advised to manage risks of reactivation of inflammation or complications from previous therapies.

Clinical Findings:

• Pulse rate – 76/min
• Respiratory rate – 18/min
• Temp -98.60℉
• BP- 120/80 mm of Hg

Systemic Examinations

Systemic examinations has been shown in table no.1

Table no:1, Systemic examination

Ophthalmic examinations

Ophthalmic examinations has been shown in table no.2.

Table no:2, Ophthalmic examination

 Diagnosis assessment:

Diagnosis:

Based on the patient’s clinical presentation, she was diagnosed with Sashopha Akshipaka in Ayurveda, which is a condition closely resembling panophthalmitis in modern medicine. This diagnosis was made by correlating her ocular complaints with classical Ayurvedic descriptions and considering the chronic inflammatory pathology observed in granulomatous uveitis.

Laboratory Investigations:

Erythrocyte Sedimentation Rate (ESR):

07/2022 – 17 mm/hr

06/2023 – 35 mm/hr

11/2023 – 46 mm/hr

05/2024 – 44 mm/hr

C-Reactive Protein (CRP): 6.67 mg/L (weakly positive)

These values indicate a progressive and ongoing inflammatory process consistent with chronic uveitis.

Ayurvedic Interpretation:

     In Ayurvedic pathology, Sashopha Akshipaka is a severe inflammatory eye disorder characterized by symptoms that correspond closely with modern descriptions of panophthalmitis and granulomatous uveitis. The term “Sashopha”implies associated with swelling, and “Akshipaka” indicates a destructive, painful inflammation of the eye.

In this patient, vitiation of Pitta and Kapha doshas was observed:

Pitta Dosha vitiation led to:

Netra Raga (reddening or congestion of the bulbar conjunctiva)

Prakasha Asahata (photophobia or intolerance to light)

Netra Shoola (ocular pain or discomfort)

Kapha Dosha vitiation was evident in:

Varthma Shopha (eyelid swelling)

Multiple joint swellings and stiffness, which are also indicative of systemic Kapha involvement

Additional classical signs of Sashopha Akshipaka noted include:

• Kandu (itching sensation)
• Upadeha (mucous discharge)
• Ashrutya (excessive tearing or lacrimation)
• Pakwa Udumbarasannibha (redness of the eye resembling the ripe Udumbara fruit, Ficus racemosa)
• Daha (burning sensation)
• Taamrata (coppery discoloration)
• Sopha (oedema)
• Nisthoda (sharp, pricking pain)
• Samharsha (horripilation or chills)

Modern-Ayurvedic Correlation:

Granulomatous uveitis is known to present with signs such as:

• Ocular pain
• Redness
• Blurred vision
• Photophobia
• Floaters

       Clinical signs: mutton-fat keratic precipitates, ciliary injection, anterior chamber flare, and cells

These manifestations closely align with the Ayurvedic descriptions above. Though histopathological confirmation is not routinely done in such cases, the chronic inflammation inferred from laboratory markers like ESR and CRP supports the clinical correlation. The presence of systemic joint involvement further strengthens the Ayurvedic interpretation involving multi-systemic dosha imbalances.

        This integrative approach to diagnosis—linking classical Ayurvedic descriptors with contemporary clinical findings—ensures both comprehensive assessment and a holistic understanding of the disease, which is critical when considering subsequent Ayurvedic management.

Timeline:

Treatments and timeline is presented on Table number 3.

Table no:3, Timeline

 Follow ups and outcomes:

Follow ups are presented in table no.4,5&6.

 Table no:4, Follow ups and outcomes

 Table no:5, Visual acuity

 Table no:6, Changes in symptoms before and after treatment

Results

            Ayurvedic treatment modalities have been employed in the management of this condition, leading to an improvement in visual acuity—6/12 in the left eye, and finger counting at 2.5 meters in the right eye, which improved to 6/36 with pinhole correction.

Detailed results are shown in table number 7.

Table no:7, Results in visual acuity.

 Discussion:

           Correlation of Granulomatous uveitis with Sashopha Akshi paka:. The current case presents as Sashopha Akshipaka (~swelling and inflammation of the eyes). Whatever disturbances occur in the body can also manifest in the eyes. The primary causes of shopha (~swelling) include the consumption of heavy, sour, salty, alkaline, sharp, oily, and cold foods, as well as improper habits such as daytime sleep and insufficient physical strength. These factors lead to the vitiation of the main doshas—pitta, rakta, and kapha. When the digestive fire is impaired, the imbalanced pitta and rakta travel upward through the body channels and reaches the eyes. In the eyes, they disturb the local pitta, affecting the conjunctiva and resulting in the manifestation of symptoms associated with the disease.

          It is being suggested that failure of the ocular immune system causes inflammation in Uveal tissue and causing derangement of the homeostatic conditions which causes auto-reactive T cells to proliferate and cause inflammation inside the eyes.   These   cells   in   the eyes, release   several inflammatory   cytokines, which   results   in   certain inflammatory changes in the form of vascular changes and cellular changes.  Blood vessels of Uveal tissues dilate   and   blood   ocular barrier will be damaged resulting in collection of inflammatory cells in anterior and posterior chamber. [13]

             The treatment principals were adopted in such a way that the therapies and medicaments which were shothahara (~anti-oedamatous), pittakaphahara (~pitta kapha pacifiers), chakshushya (~eye health promotors) and srotoshodhakara (~body channels cleansers) were selected. The root cause of the disease lies in the formation of amavastha (~condition of free radicals formation), which results from the imbalance of vitiated pitta and kapha. The Kaya shodhana (~detoxification) eliminates the underlying free radicals from the ocular tissues along with appetizers and digesters to improve the status of Dhatvagni (~specific fires of body tissues) and to phagocytose the necrosed cellular components.

          The Sneha Pana (~oral intake of medicated ghee) has lipid-based formulations infused with medicated drugs which reaches the target tissues and facilitates the removal of toxins, causing utkleshana (exfoliation) of the tissues. The formulation, Pancha Tiktaka Guggulu Ghruta, which contains bitter herbs, primarily works to address fluid imbalances in the body. Its therapeutic effects target various bodily fluids such as Kleda (~bodily moistures), Medo(~fatty tissues), Vasa(~adipose tissue), Majja(~essence of bone), Laseeka (~interstitial fluids), Pooya(~pus), Sweda(~sweat), Mutra(~urine), and Pitta, and it supports the reduction of excess fluids. The treatments like Abhyanga (~external oleation) and Swedana(~sudation), the toxins are directed towards the digestive system for elimination, either through excretion or sweating. These therapies likely support the rejuvenation of damaged retinal and macular cells, which helps restore and maintain normal vision post-treatment. Virechana (~medicated purgation) is a therapeutic process that helps eliminate the aggravated doshas, particularly those that are disturbed or exfoliated in the body. Trivrut Avalehya, which has a balancing effect on both Pitta and Kapha, is considered a gentle and effective form of medicated purgation.

               Local treatments such as Netra Parisheka (~eye irrigation) are beneficial for addressing localized imbalances, specifically Pitta and Kapha, within the eyes.[14] These treatments help soothe and balance the doshas in the eye region.

             Nasya(~administration of therapeutic oils or herbal preparations through the nasal passages), is believed to promote the circulation of Prana (life energy) in the head. It helps to improve blood flow to the eyes, potentially supporting better eye health and alleviating symptoms related to various eye conditions. The cooling properties of the drugs used in Nasya are particularly effective in reducing Pitta dosha.

          The ingredients of Panchatikta guggulu Ghruta is specifically beneficial for balancing Pitta and Kapha dosha and have tendency to cross the blood-ocular barrier and thereby nourish the ocular tissues Additionally, Putapaka (~medicated juice) is specifically effective in managing chronic eye diseases and helps in overcoming macular edema.  Jaloukavacharana (~leech therapy) in Uveitis not only accelerates the healing process, but also avoids the recurrence and the formation of synechiae. Thus the application of leech in this case contributes to the rapid regression of signs and symptoms such as pain, redness, congestion and aqueous cells. Leech therapy is having an important role in treating Pittaja and Raktaja eye disorders by doing Raktashodhana(~blood purification). When leaches are applied over the sites they inject biologically active substances through saliva, Calin, Eglin have anti-inflammatory properties that helps in arresting inflammation, vasodilators like acetylcholine, histamine increases the blood flow at the affected area and during sucking of blood and hyaluronidase facilitates the penetration and diffusion of pharmacological active substances into the deeper tissue.

            Mahamanjishtadi Kwatha is commonly used in the treatment of eye disorders, while Trayodashanga Guggulu primarily addresses immune-related eye conditions. Some ingredients in Arogya Vardhini, such as Haritaki (Terminalia chebula) and Amalaki (Indian gooseberry), are known for their strong antioxidant and anti-inflammatory effects, which can support overall eye health.[15] The combination of Saptamruta lauha, Mahatriphala Ghruta, and Yashada Bhasma mix with honey and milk helps protect the eye cells from oxidative stress and damage caused by free radicals. Oxidative damage is often linked to eye diseases like cataracts, macular degeneration, and diabetic retinopathy. Additionally, Yashada Bhasma’s anti-inflammatory properties can reduce inflammation and prevent further tissue damage in the eyes.

Patient perspective :

          Informed Consent: Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. The patient was informed that personal details would be kept confidential and efforts would be made to ensure anonymity, although complete anonymity cannot be guaranteed.

 Conclusion

          Ayurvedic interventions, when combined with conventional treatment strategies, can play a significant role in managing granulomatous non-infectious posterior uveitis. Further research and controlled studies are needed to substantiate these findings and explore the potential for Ayurvedic therapies in the management of uveitis.

References:

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[2] Jakubzick C, Gautier EL, Gibbings SL, Sojka DK, Schlitzer A, Johnson TE, Ivanov S, Duan Q, Bala S, Condon T, van Rooijen N, Grainger JR, Belkaid Y, Ma’ayan A, Riches DW, Yokoyama WM, Ginhoux F, Henson PM, Randolph GJ. Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity. 2013;39(3):599-610. doi:10.1016/j.immuni.2013.07.007.

[3] Crouser ED, White P, Caceres EG, Julian MW, Papp AC, Locke LW, Sadee W, Schlesinger LS. A Novel In Vitro Human Granuloma Model of Sarcoidosis and Latent Tuberculosis Infection. Am J Respir Cell Mol Biol. 2017;57(4):487-498. doi:10.1165/rcmb.2017-0022OC.

[4] Locke LW, Schlesinger LS, Crouser ED. Current Sarcoidosis Models and the Importance of Focusing on the Granuloma. Front Immunol. 2020;11:1719. doi:10.3389/fimmu.2020.01719.

[5] Broos CE, van Nimwegen M, Hoogsteden HC, Hendriks RW, Kool M, van den Blink B. Granuloma formation in pulmonary sarcoidosis. Front Immunol. 2013;4:437. doi:10.3389/fimmu.2013.00437.

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[7] PaçKisaarslan A, Sözeri B, Şahin N, Özdemirçiçek S, Gündüz Z, Demirkaya E, Berdeli A, Sadet Özcan S, Porazoğlu H, Düşünsel R. Blau Syndrome and Early-Onset Sarcoidosis: A Six Case Series and Review of the Literature. Arch Rheumatol. 2020;35(1):117-127. doi:10.46497/ArchRheumatol.2020.7047.

[8] Rosé CD, Doyle TM, McIlvain-Simpson G, Coffman JE, Rosenbaum JT, Davey MP, Martin TM. Blau syndrome mutation of CARD15/NOD2 in sporadic early onset granulomatous arthritis. J Rheumatol. 2005;32(2):373-375. PMID:15693002.

[9] National Organization for Rare Disorders (NORD). Posterior Uveitis. Available from: https://rarediseases.org/rare-diseases/posterior-uveitis/. Accessed April 2025.

[10] Khurana AK. Comprehensive Ophthalmology. 6th ed. New Delhi: Jaypee Brothers Medical Publishers (P) Ltd.; Reprint 2015. p.150.

[11] Babu BM, Rathinam SR. Intermediate uveitis. Indian J Ophthalmol. 2010;58(1):21-27. doi:10.4103/0301-4738.58468.

[12]Sushrutasamhita, Uttaratantra, Sarvagatarogavijnaneeyadhyaya, 6/33. Available from: http://niimh.nic.in/ebooks/esushruta (Accessed on 15 March 2025).

[13] Myron Yanoff, MD and Jay S. Duker, MD. Ophthalmology, 4th Edition. Publication Date: 16-12-2013. ISBN: 9781455739844.

[14] Sushrutasamhita, Uttaratantra, Kriyakalpadhyaya, 18/44-48. Available from: http://niimh.nic.in/ebooks/esushruta (Accessed on 15 March 2025).

[15] Govind Das. (2016). Bhaishajya Ratnavali (Siddhinandan Mishra, Ed., Shvitra Chikitsa, Chapter 53, shloka 88). Varanasi: Chaukhambha Surbharati Prakashan.