Delhi Journal of Ophthalmology

Response of Autologous Serum Supratarsal Injection in Patients of Vernal Keratoconjunctivitis in Longterm Followup

Ritu Agarwal, Jai Shree Murli Manoher
Jawaharlal Nehru Medical College, Ajmer, Rajasthan, India

Corresponding Author:

Ritu Agarwal
Department of Ophthalmology 
Jawaharlal Nehru Medical College,
Ajmer, Rajasthan, India
Email id: agarwal.dr.ritu.09@gmail.com

Received: 22-JAN-2019

Accepted: 19-SEP-2019

Published Online: 27-FEB-2020

DOI:http://dx.doi.org/10.7869/djo.500

Abstract
Purpose: To study the response of 0.1 ml autologous serum supratarsal injection in patients of vernal keratoconjunctivitis in their long term followup. 
Materials and Methods: This prospective, nonrandomized study was carried out in 50 patients of either sex and any age suffering from vernal keratoconjunctivitis. Previous medications were discontinued for period of 15 days before commencing serum injection. 0.1 ml of autologous serum was injected in each eye supratarsaly. Injection was repeated every week for 8 weeks and follow up of all patients was done at one month, three months, six months and one-year interval. 
Results: Significant improvements in symptoms and some of the signs were achieved. Improvement was significant even after discontinuation of treatment. No additional medications were required. 
Conclusions: 0.1 ml supratarsal injection of autologous serum is an effective alternative treatment in vernal for long term and without any adverse effects.

Keywords :Vernal Keratoconjunctivitis, autologous serum, long term

Introduction
Vernal keratoconjunctivitis is a bilateral inflammatory disorder of conjunctiva and cornea,1 commonly in first and second decade.2
Topical corticosteroids are the mainstay of therapy. However prolonged use may result in glaucoma, cataract, dry eye and secondary infections.3 Therefore serious side effects with steroids, incomplete amelioration of symptoms with other drugs and requirement of long term instillation of drugs, necessitated the study of other therapeutic agents.
In vernal keratoconjunctivitis increase of Th2 occurs, that leads to overactivation of Th2 cells giving rise to hypersensitivity reaction and autologous serum acts mainly by shifting of the Th2 cytokine profile to Th1.4

Material and Methods
This quasi experimental study was carried out in 50 patients of either sex and any age suffering from vernal keratoconjunctivitis. VKC was diagnosed on the basis of the presence of itching, ropy discharge, photophobia, papillae on upper tarsal conjunctiva and limbal changes. Previous oral or topical medications were discontinued for period of 15 days before commencing autologous serum injection. Complete ophthalmic examination was performed including details of symptoms, visual acuity and slit lamp biomicroscopy. Family or personal history of allergic disorders was taken. Symptoms were recorded and graded according to [Table-1] (Tahir Masaud et al, 2011).5

Table 1: Grading of symptoms


Ocular clinical signs were graded according to [Table-2] (Tahir Masaud et al, 2011).5

Table 2: Grading of signs


Patients were informed of the aim and informed consent was taken before procedure. Autologous serum was prepared by withdrawing 5 ml of the venous blood from antecubital vein and centrifuging it at 2000 rpm for 10 min. The supernatant serum was removed and 1 ml of serum was taken. Supratarsal injection was given under topical anaesthesia using 26 G needle and 0.1 ml of autologous serum was injected in each eye. Injection was repeated every week for 8 weeks and follow up of all patients was done at one month, three months, six months and one-year interval. 

Results
Our observations are based on 1 year follow up study of 50 patients diagnosed as cases of vernal keratoconjunctivitis. There was male predominance with male:female ratio 7.3:1. Mean age was 12.34 years and SD was 4.98. The minimum age was 4 years and maximum age was 25 years. Most common in summer months of April-June, however disease was seen throughout the year. Symptoms such as itching, redness and watering were present in all the cases, photophobia was present in 52% cases and ropy discharge in 34% of patients.
Signs such as conjunctival hyperaemia was present in 72% of patients, papillary hypertrophy at superior tarsus in 48%, gelatinous limbal ring in 98%, horner trantas dots in 26% and corneal involvement in form of superficial punctuate keratopathy was seen in only 4% of patients.
5 patients (3 male and 2 female) losts subsequent follow ups after first injection.
Symptoms [Table-3] - There was highly significant improvement in the symptoms after 8 supratarsal autologous serum injections and in long term follow up till 1 year.

Table 3: Improvement in the symptoms after 8 supratarsal autologous serum injections and in long term follow up till 1 year


On day 0, 45 patients complained of itching, redness and watering, after 3 months of treatment with supratarsal autologous serum injection, improvement was seen in 88.9%, 82.2% and 88.9% of patients respectively but recurrence of itching and redness was seen in 11.1% and of watering in 8.9% of patients at 1 year, but still improvement was highly significant (p<0.001).
Initially, 26 patients complained of photophobia, after 3 months of treatment improvement was seen in 46.2% of patients, but recurrence of photophobia was seen in 15.4% and at 1 year, still improvement was significant (p<0.01).
Initially, 17 patients had ropy discharge, after 3 months of treatment improvement was seen in 58.8% of patients but recurrence seen in 11.8% of patients at 1 year, still improvement was significant (p=0.01).
Signs [Table-4] - Significant improvement was found only in conjunctival hyperemia and gelatinous limbal ring [Figure-1]. Improvement in other signs of vernal keratoconjunctivitis were not significant.
1. On day 0, 32 patients had conjunctival hyperaemia, after 3 months of treatement with supratarsal autologous serum injection improvement was seen in 27 (84.4%) patients, but recurrence was seen in 2 (6.3%) patients at 1 year, still improvement was highly significant in long term (p<0.001). 
2. On day 0, 22 patients had papillary hypertrophy, after 3 months of treatement improvement was seen in 4 (18.2%) patients, recurrence seen in 1(4.5%) patient at 1 year, improvement was not significant . 
3. On day 0, 44 patients had gelatinous limbal ring, after 3 months of treatement improvement seen in 20 (50%) patients, but recurrence noted in 5 (12.5%) patients at 1 year, still improvement was highly significant in long term (p<0.001). 
4. 13 patients had horner trantas dots, improvement was seen in 3(23.1%) patients after months but recurred in all at 1 year.
5. No improvement was seen in superficial punctuate keratopathy.

Table 4: Improvement in the signs after 8 supratarsal autologous serum injections and in long term follow up till 1 year


Discussion
VKC is a chronic, bilateral, seasonally exacerbated, allergic inflammation of the tarsal conjunctiva, bulbar conjunctiva, or both. More common in children and young adults with known atopy. The age incidence is more commonly between 6 to 20 years with a peak incidence between the ages of 11 and 13 years. There is stronger predilection for men being affected two or three times more frequently than women. Typically presents with itching, hyperaemia, photophobia, watering and ropy discharge. Itching was the most common symptom.
Three typical forms are seen Palpebral or Tarsal, Limbal and Mixed. Palpebral form of disease is characterized by conjunctival hyperaemia and papillary hypertrophy. In limbal form wall of gelatinous thickening at the limbus, mucoid nodules and Horner-Trantas dots are characteristic findings. In mixed form both palpebral and limbal signs are observed to varying degrees. Corneal findings include pseudogerontoxon, punctuate epithelial keratitis, corneal shield ulcers and corneal ectasia rarely.6,7
VKC is a manifetstation of a hypersensitivity response in the conjunctiva and cornea in which exogenous allergens or autosensitisation acts as the exciting agent and in which physical factors such as warmth and light play determining part, occurring preferentially in young individuals showing an endocrine vagotonic imbalance.8 The imbalance between Th2 and Th1 lymphocytes leads to overactivation of Th2 cells giving rise to hyperactivity against substances that commonly comes in contact with mucosa.
Although there is variety of drugs being used for vernal keratoconjunctivitis, none of the therapy is ideal with no or minimal side effects. However topical use of steroids is most accepted treatement of vernal keratoconjunctivitis, but it has certain disadvantages also such as rise of intraocular pressure, lenticular changes and corneal complications like keratitis.
A number of newer therapeutic agents have been attempted in treatement of vernal keratoconjunctivitis. They include topical non steroidal anti-inflammatory agents, topical mast cell stabilizers {nedocromil,lodoxamide (Caldwell 1992)},9 topical immunomodulators {cyclosporine}, topical antihistaminics {Levocabastine} and ganglioside derivatives {Miprogoside (Centofanti M et al, 1996)},10 supratarsal injection of steroids (Holsclaw et al, 1996).11 and cyclosporine (Menna V,2004).12 However, most of these newer treatement modalities have been found relatively ineffective.
The pathogenesis of vernal keratoconjunctivitis suggests that the therapy should be targeted towards reduction of Th2 activity and the major mechanism by which autologous serum acts in VKC is by shifting of the Th2 cytokine profile to Th1.13,14 Serum also exhibits characteristics properties which are very similar to those of tears regarding pH and osmolarity, this helps by providing symptomatic relief.15
The present study was conducted to evaluate the efficacy and safety of 0.1 ml autologous serum injected supratarsaly in patients of vernal keratoconjunctivitis and to see the recurrence of spring catarrah in long term follow up. The treatment was effective in alleviating the ocular symptoms of itching (p<0.001), redness (p<0.001), watering (p<0.001), photophobia (p<0.01) and ropy discharge (p=0.01), even after 10 months of discontinuation of treatement. Amongst the signs, conjunctival hyperaemia and gelatinous limbal ring was reduced significantly (p<0.001) [Figure 1 and Figure 2] but other signs such as papillary hypertrophy, horner trantas dots and superficial punctuate keratopathy showed little or no improvement no significant complications were observed during the trial.

Figure 1: Figure showing improvement in conjunctival hyperemia and corneal limbal oedema

Figure 2: Figure showing improvement in gelatinous limbal ring and mucoid nodules

Conclusion
By analyzing the results of our study we have come to the conclusion that use of 0.1 ml supratarsal injection of autologous serum is an effective alternative treatment in vernal keratoconjunctivitis with decrease of signs and symptoms for long term and without adverse effects of conventional therapies.

References
  1. Beigelman MN. Vernal Conjunctivitis. University of Southern California Press: Los Angeles, 1950.
  2. De Smedt, S., G. Wildner, and P. Kestelyn, Vernal keratoconjunctivitis: an update. Br J Ophthalmol 2013. 97(1): 9-14.
  3. Havener WH. Corticosteroid therapy. In: Ocular Pharmacology. St. Louis: CV Mosby 1983; 433-500. 
  4. Abu El-Asrar AM, Van den Oord JJ, Geboes K, et al: Immunopathological study of vernal keratoconjunctivitis. Graefes Arch Clin Exp Ophthalmol 1989; 227:374.
  5. Tahir Masaud Arbab, Manzoor A Mirza. Topical Use of Cyclosporine in the Treatment of Vernal Keratoconjunctivitis. Pak J Ophthalmol 2011; 27(3).
  6. Kumar S. Vernal keratoconjunctivitis: a major review. Acta Ophthalmologica 2009; 87(2): 133-147.
  7. Bonini S, Bonini S, Lambiase A, Marchi S, Pasqualetti P, Zuccaro O, et al. Vernal keratoconjunctivitis revisited: a case series of 195 patients with long-term followup. Ophthalmology 2000; 107: 1157–1163.
  8. Bonini S, Lambiase A, Schiavone M, Centofanti M, Palma LA, Bonini S. Estrogen and progesterone receptors in vernal keratoconjunctivitis. Ophthalmology 1995; 102:1374–1379.
  9. Caldwell DR, Verin P, Hartwich-Young R, Meyer SM, Drake MM. Efficacy and safety of lodoxamide 0.1% vs cromolyn sodium 4% in patients with vernal keratoconjunctivitis. Am Jophthalmol 1992; 113(6):632-7.
  10. Centofanti M, Schiavone M, Lambiase A, Taffara M, Giuffrida S, Bonini S. Efficacy of mipragoside ophthalmic gel in vernal keratoconjunctivitis. Eye 1996; 10(4):422-4.
  11. Holsclaw DS, Whitcher JP, Wong IG, Margolis TP. Supratarsal injection of corticosteroid in the treatment of refractory vernal keratoconjunctivitis. Am J ophthalmol 1996; 121(3):243-9.
  12. Menna V. Role of topical and supratarsal injection of cyclosporine A in the treatment of vernal keratoconjunctivitis. Thesis 2004.
  13. Alvarado-Flores E, Avalos-Diaz E, Diaz L, Herrara-Esparza R. Anti-idiotype antibodies neutralize in vivo the blistering effect of pemphigus foliaceous IgG. Scand J Immunol 2001; 53:254-8.
  14. Staubach P, Onnen K, Vonend A, Metz M, Siebenhaar F, Tschentscher I, et al. Autologous whole blood injection to patients with chronic urticaria and a positive autologous serum skin test: A placebo-controlled trial. Dermatology 2006; 212:150-9.
  15. Lagnado R, King AJ, Donald F, Dua HS. A protocol for low contamination risk of autologous serum drops in the management of ocular surface disorders. Br J Ophthalmol 2004; 88(4):464-5.

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Agarwal R, Manoher JSMResponse of Autologous Serum Supratarsal Injection in Patients of Vernal Keratoconjunctivitis in Longterm Followup.DJO 2019;30:31-34

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Agarwal R, Manoher JSMResponse of Autologous Serum Supratarsal Injection in Patients of Vernal Keratoconjunctivitis in Longterm Followup.DJO [serial online] 2019[cited 2020 Mar 31];30:31-34. Available from: http://www.djo.org.in/articles/30/2/Response-of-Autologous-Serum-Supratarsal-Injection-in-Patients-of-Vernal-Keratoconjunctivitis-in-Longterm-Followup.html