Vernal keratoconjunctivitis (VKC) is a recurrent, bilateral allergic inflammation of the conjunctiva ^[1].  It typically appears in episodes that are often periodic and recur seasonally, especially during spring and summer, but can become a year-round (perennial) condition over time. VKC is a subtype of allergic conjunctivitis, with other types including perennial and seasonal rhino conjunctivitis, atopic keratoconjunctivitis, and giant papillary conjunctivitis ^[2].

VKC is classified based on the area of ocular involvement into palpebral, limbal, and mixed forms:

1. Palpebral Vernal Keratoconjunctivitis: This form affects the upper tarsal conjunctiva, where inflammation can lead to significant corneal disease due to its close association with the corneal epithelium.
2. Limbal Vernal Keratoconjunctivitis: Primarily involving the bulbar conjunctiva near the limbus, this type is more commonly seen in Black and Asian populations.
3. Mixed Vernal Keratoconjunctivitis: This variant exhibit features of both the palpebral and limbal forms ^[3].

Vernal keratoconjunctivitis (VKC) is a recurrent, bilateral disorder, more frequently observed in males and commonly appearing after the age of five. Most cases experience remission as patients grow, typically resolving by puberty, although some may progress to develop atopic keratoconjunctivitis. VKC is more prevalent in warm, dry climates and exhibits seasonal variation, with peak incidence in the spring and summer. As the disease becomes chronic, symptoms may persist throughout the year, increasing the likelihood of a perennial presentation ^[4].

Many VKC patients have a history of atopy, and family history is positive for atopy in approximately 49% of cases, suggesting a potential genetic component. In addition to personal allergy history, other risk factors include male gender, close contact with animals, and increased exposure to dust and sunlight ^{[5 – 7]}.

Both IgE-mediated and cell-mediated immune responses are thought to drive VKC exacerbations. Activated eosinophils play a significant role, with studies, including Gabrielides’, consistently finding eosinophils in conjunctival scrapings of VKC patients. Type 4 hypersensitivity, mediated by CD4 T helper cells, has also been implicated, with studies highlighting the involvement of interleukins (IL-4, IL-5, IL-13) and fibroblast growth factors. Additionally, cytokines and chemokines are often overexpressed in the conjunctiva of VKC patients ^[8].

Topical corticosteroids, particularly low-absorption options like fluorometholone, loteprednol, and rimexolone, are considered safe choices for treating VKC. In severe cases, stronger steroids like dexamethasone or betamethasone may be required. However, topical steroids should be tapered quickly and monitored closely for increases in intraocular pressure ^[2].

For patients with recurrent episodes, steroid-sparing agents offer a safer alternative. Topical immunomodulators such as cyclosporine (0.05-2%) and tacrolimus (0.1%) are commonly used, as they reduce inflammatory cytokines. Cyclosporine, for instance, works by blocking T-helper 2 cells, which inhibits lymphocyte proliferation. It also reduces histamine release from mast cells and basophils, and decreases conjunctival fibroblast proliferation and interleukin-1b production ^[9].

In some VKC patients, systemic treatments may be necessary, especially if they have associated atopic conditions like asthma or atopic dermatitis. Drugs like montelukast, a leukotriene receptor inhibitor, are effective in asthma management and have shown benefits in VKC by reducing symptoms and inflammation. Another monoclonal antibody, dupilumab, targets interleukin-4 receptors and is commonly used for atopic dermatitis, with positive effects on VKC as well. Omalizumab, an anti-IgE monoclonal antibody, has also been used off-label in difficult-to-treat VKC cases ^{[10 – 11]}.

Sodium cromoglycate is a mast cell stabilizer that helps prevent type I allergic reactions, making it effective in reducing ocular signs and symptoms associated with hay fever, both acute and chronic, as well as vernal keratoconjunctivitis. Additionally, it may reduce the need for supplementary oral antihistamines. Sodium cromoglycate eye drops are commonly prescribed for managing allergic eye conditions and allergic rhinitis ^{[12 – 14]}.

llodoxamide, an antiallergic agent, in treating allergic conjunctivitis. This double-blind, randomized, placebo-controlled, parallel-group trial included 30 patients with seasonal allergic conjunctivitis caused by grass pollen, conducted during the pollen season. Participants received lodoxamide tromethamine 0.1% eye drops or placebo drops, applied three times daily in each eye for 4 weeks. Clinical and cytological assessments were conducted at baseline and after 4 weeks. At the trial’s end, only the lodoxamide group showed significant clinical improvement, with reduced inflammatory cells, especially eosinophils. No serious side effects were observed, indicating that lodoxamide is effective and safe for treating pollen-induced allergic conjunctivitis through its reduction of inflammatory infiltrate.

The study was conducted in the Outpatient Department of Ophthalmology at tertiary care hospital the study were carried over a period of 3 months from February to April 2021, after taking approval from the institutional ethics committee. Written informed consent form was taken form the patients or patient attendant.  After taking inform consent, past and present history of the patient was taken. The clinical eye examination was done on all 156 patients among them 150 patients were included in the study 6 patients missed from the study. The symptoms of disease, cause of disease and WBC count were missed for all the patients before and after the study.

Inclusion Criteria

1. Patients aged group between 5–15 years attending the OPD at tertiary care hospital.
2. Patients able to adhere to the follow-up schedule.
3. Patient or patient attendant ready to give inform consent
4. Patient having financial support for buying medicine.
5. Patients not on any ocular drugs.

Exclusion Criteria –

1. Patients less than 5 years of age.
2. Patient waring contact lens during the study period.
3. Patients having or had active ocular infections or pathological conditions.
4. Patients with any ocular disorders.
5. History of ocular surgery within the past 3 months.
6. Patient or patient attendant not ready to give inform consent form.
7. Patient taking ocular drug that is used for the study.

Patients were randomly divided based on chit method into three groups Group A patients were treated with sodium cromoglycate, group B patients were treated with Lordoxamide and group C patients were treated with Loteprednol with one drop drug is administered to the affected eye twice daily for 8 weeks.

The ocular signs such as conjunctival hyperemia, papillary hypertrophy and other ocular symptoms were estimated. The grading of symptoms was done based on absence of sign – grade O, Mild sign grade 1, moderate sign – grade 2 and severe sign - grade 3.

Statistical analysis

The date collected from the OPD were noted and tabulated in ms excel sheet and the data was analysed by using SPSS Software version 16. Unpaired t test was conducted with three groups p value less than 0.05 stated as significant and p value less than 0.005 stated as highly significant.

Figure 1 & 2 shows the age and gender distribution of the study population. Of the 150 patients, 108 (72%) are between 5 and 10 years old, while 42 (28%) are between 11 and 15 years old. Among the participants, 98 (65.3%) are male, and 52 (34.66%) are female.

Table 0, Shield ulcer (94.66%) is the major symptoms observed in Vernal keratoconjunctivitis (VKC) patients followed by sticky mucous discharge (88.00%) patients respectively.

Table 02 In an infectious condition there will be an elevation of white blood cell count and CRP levels. There is a increase in neutrophils, eosinophils and CRP. After treatment there is increase improvement in neutrophils and significant in basophils and CRP at 3^rd visit (0.005) 

Table 3 mean average CRP levels was observed in all three treatment groups followed by eosinophils and neutrophils. 

Figure 1 Gender variation in study groups

Figure 2 Age difference in study population.

Table No 01 – Symptoms observed in Vernal keratoconjunctivitis (VKC) patients.

Figure 03 percentage variation in symptoms in all the vernal keratoconjunctivitis patients.

Table 2 Average Number of patients having elevated & Controlled blood parameter in Vernal keratoconjunctivitis after 3 visits in group A, B, & C.

Table 3– Improvement in blood parameters in vernal keratoconjunctivitis patients in all treatment groups.

Table 4– Tabular column represents the mean average changing in itching score in all three groups.

Table 5– Tabular column represents the mean average changing in ocular damage score in all three groups.

Table 6 – Tabular column represents the mean average changing in Conjunctival hyperaemia score in all three groups.

Table 7– Tabular column represents the mean average changing in Papillary Hypertrophy score in all three groups.

VKC is an ocular allergic disease affecting the bulbar and tarsal conjunctiva of eye’s. there is a increase in IgE and T-cell responses in blood leading to chronic inflammation, increased in eosinophil, lymphocytes and some structural cell changes. Drugs like antihistamines, corticosteroids was the drug of choice for treatment of VKC.

In this research study majority of the patients were male (65%) followed by female (35%) with the age group between 5 – 10 followed by 11 - 15 showing statically insignificant (>0.05) (Figure 01 & 02).

As per the symptoms of VKC patient, Out of  150 patients 142 shield ulceration in followed by Sticky mucous discharge 132 (88.00%), Photophobia 88 (58.66%), Hornertrantas spots 81 (54.00%), Keratoconus 62 (41.33%), Cobblestone appearance 35 (23.33 %), Superficial punctate keratitis 32 (21.33 %), Chemosis 28 (18.66 %) and Pseudogarontoxon 12 (08.00%) respectively. 

As VKC is a allergic disease there will be a changes in blood parameter. In our study we estimated neutrophils, eosinophils and CRP levels. After prescribing drug the patents were told to visit the hospital for every week for 3 weeks. Each week is named as a visit (1^st , 2^nd & 3^rd  visits) in all three groups. There is no significant changes was observed in neutrophil in all group (>0.005) significant improvement was observed in eosinophil and CRP levels at 3^rd visit in all three groups (p<0.005) respectively.  The mean average reduction in number of patients was seen in CRP levels followed by eosinophils and neutrophils at 2^nd vs 3^rd visit in all three groups respectively. 

the score of allergies was done based on scoring procedure. No symptoms - 0 score, mild – 1score, Moderate – 2 score and Severe – 3 score. As per the itching score before starting of treatment the average score in group A was 2.62±1.42, group B 2.36±1.26 and group C 2.32±1.16 showing statically in significant (p 1.248) . But after 1^st visit there is a change in average score to 2.58±1.21 in group A, 2.12 ±1.12 in group B and 2.26±0.86 in group C showing statically insignificant (p 1.042). At 2^nd visit there is change in score to 2.26±0.86 in group A, 1.94±0.74 group B and group C 2.10±0.62 was statically in significant (p 0.194) and at 3^rd visit there is a change in score to 2.16±0.42 at group A, 1.64±0.52 in group B and in group C 1.84±0.34 showing statically insignificant (p 0.108) respectively.

As per the Ocular damage before starting of treatment the average score in group A was 2.84±2.94, group B 2.78±2.42 and group C 2.68±2.26 showing statically in significant (p 1.846). But after 1^st visit there is a change in average score to 2.14±2.04 in group A, 2.32±2.04 in group B and 2.10±2.04 in group C showing statically insignificant (p 1.244). At 2^nd visit there is change in score to 1.64±1.16 in group A, 1.52±1.06 group B  and group C 1.42±1.01 was statically significant (p 0.050) and at 3^rd visit there is a change in score to 0.64±0.86 at group A, 0.82±0.74 in group B and in group C 0.94±0.42 showing statically insignificant (p 0.026) respectively.

As per the Conjunctival hyperaemia before starting of treatment the average score in group A was 2.94±2.32, group B 2.84±2.10 and group C 2.78±1.84 showing statically in significant (p 0.214). But after 1^st visit there is a change in average score to 2.66±1.23 in group A, 2.56±1.42 in group B and 2.44±1.02 in group C showing statically insignificant (p 0.186). At 2^nd visit there is change in score to 1.85±0.89 in group A, 1.64±0.64 group B and group C 1.42±0.56 was statically in significant (p 0.089) and at 3^rd visit there is a change in score to 1.12±0.04 at group A, 1.22±0.06 in group B and in group C 1.06±0.02 showing statically significant (p 0.050) respectively.

As per the Papillary Hypertrophy before starting of treatment the average score in group A was 2.14±1.24, group B 2.01±1.89 and group C 2.78±1.842.12±0.84 showing statically in significant (p 1.864). But after 1^st visit there is a change in average score to 1.26±1.01 in group A, 1.24±1.24 in group B and 1.15±0.01 in group C showing statically insignificant (p 1.024). At 2^nd visit there is change in score to 1.18±0.14 in group A, 0.21±0.15 group B and group C 0.14±0.01 was statically in significant (p 0.005) and at 3^rd visit there is a change in score to 0.084±0.04 at group A, 0.10±0.01 in group B and in group C 0.023±0.21 showing statically significant (p 0.005) respectively.

In a study by S. Bonini et al. (1997) ^[16], lodoxamide significantly reduced tryptase levels (P < 0.01), neutrophils (P < 0.04), and eosinophils (P < 0.01) in tear fluid, and notably inhibited ocular itching (P < 0.02) compared to placebo.

Dial Das et al. (2017) ^[17] conducted a study involving 80 diagnosed cases of VKC, consisting of 56 males (70%) and 24 females (30%). Patients who had previously received treatment for VKC or had other types of eye allergies were excluded. Participants were divided into two groups: Group A, with 40 patients using topical lodoxamide drops, and Group B, with 40 patients using sodium cromoglycate drops. There was no significant demographic difference between the groups (p > 0.05). The findings showed that lodoxamide in Group A had a significantly better adverse effect profile compared to sodium cromoglycate in Group B (p < 0.001).a

Vernal keratoconjunctivitis (VKC) is an allergic eye disease. For treatment, antiallergic drugs can be prescribed. The current study shows that all drugs tested provided improvement in VKC management, with mast cell stabilizers demonstrating the most significant improvement

1. Oray M, Toker E. Tear cytokine levels in vernal keratoconjunctivitis: the effect of topical 0.05% cyclosporine a therapy. Cornea. 2013 Aug;32(8):1149-54.
2. Vichyanond P, Kosrirukvongs P. Use of cyclosporine A and tacrolimus in treatment of vernal keratoconjunctivitis. Curr Allergy Asthma Rep. 2013 Jun;13(3):308-14.]
3. Barot RK, Shitole SC, Bhagat N, Patil D, Sawant P, Patil K. Therapeutic effect of 0.1% Tacrolimus Eye Ointment in Allergic Ocular Diseases. J Clin Diagn Res. 2016 Jun;10(6):NC05-9.
4. Wan Q, Tang J, Han Y, Wang D, Ye H. Therapeutic Effect of 0.1% Tacrolimus Eye Drops in the Tarsal Form of Vernal Keratoconjunctivitis. Ophthalmic Res. 2018;59(3):126-134. [P ubMed: 28803239]
5. Leonardi A. Management of vernal keratoconjunctivitis. Ophthalmol Ther. 2013 Dec;2(2):73-88. [ PMC free article: PMC4108143] [ PubMed: 25135808]
6. Alemayehu AM, Yibekal BT, Fekadu SA. Prevalence of vernal keratoconjunctivitis and its associated factors among children in Gambella town, southwest Ethiopia, June 2018. PLoS One. 2019;14(4):e0215528. [ PMC free article: PMC6472775] [ PubMed: 30998721]
7. Leonardi A. Vernal keratoconjunctivitis: pathogenesis and treatment. Prog Retin Eye Res. 2002 May;21(3):319-39. [ PubMed: 12052387]
8. Bremond-Gignac D, Donadieu J, Leonardi A, Pouliquen P, Doan S, Chiambarretta F, Montan P, Milazzo S, Hoang-Xuan T, Baudouin C, Aymé S. Prevalence of vernal keratoconjunctivitis: a rare disease? Br J Ophthalmol. 2008 Aug;92(8):1097-102.
9. Bielory L, Bonini S, Bonini S. Allergic eye disorders. Clin Allergy Immunol. 2002; 16:311 23.
10. Pucci N, Novembre E, Cianferoni A, Lombardi E, Bernardini R, Caputo R, Campa L, Vierucci A. Efficacy and safety of cyclosporine eyedrops in vernal keratoconjunctivitis. Ann Allergy Asthma Immunol. 2002 Sep;89(3):298-303.
11. Leonardi A, Borghesan F, DePaoli M, Plebani M, Secchi AG. Procollagens and inflammatory cytokine concentrations in tarsal and limbal vernal keratoconjunctivitis. Exp Eye Res. 1998 Jul;67(1):105-12.
12. Sorkin EM, Ward A. Ocular sodium cromoglycate. An overview of its therapeutic efficacy in allergic eye disease. Drugs 1986; 31:131‑48.
13. Collum LM, Fitzsimon S, Hillery M, Collum A, Power WJ, Pelikan Z, et al. Twice daily 4% Sodium Cromoglycate vs. 2% Sodium Cromoglycate used four times daily in seasonal (grass pollen) allergic conjunctivitis. Doc Ophthalmology 1992; 82:267‑77.
14. Lejeune M, Lefebvre PP, Delvenne P, El‑Shazly AE. Nasal sodium cromoglycate (Lomusol) modulates the early phase reaction of mild to moderate persistent allergic rhinitis in patients mono‑sensitized to house dust mite: A preliminary study. Int Immunopharmacology 2015; 26:272‑6.
15. M. Cerqueti, V. Ricca, M.A. Tosca, S. Buscaglia, G. Ciprandi; Lodoxamide Treatment of Allergic Conjunctivitis. Int Arch Allergy Immunol1 February 1994; 105 (2): 185–189.
16. Bonini S, Schiavone M, Bonini S, Magrini L, Lischetti P, Lambiase A, Bucci MG. Efficacy of lodoxamide eye drops on mast cells and eosinophils after allergen challenge in allergic conjunctivitis. Ophthalmology. 1997 May;104(5):849-53. doi: 10.1016/s0161-6420(97)30223-1. PMID: 9160033.
17. Dial Das, Jai Perkash et al. Assessment of Adverse Effects of Lodoxamide and Sodium Cromoglycate during the Keratoconjunctivitis. PJMHS.2017;11(3):926-929