• History of trauma/injury with vegetative matter
• History of contact lens use
• Past history of viral keratitis
Slit lamp evaluation suggestive of poor ocular surface, presence of corneal infiltrates and hypopyon
Likelihood of response to intensive topical steroids is related to the laterality of involvement. Nevertheless not all ulcers respond to topical steroid therapy and as opposed to other types of PUK, Mooren’s ulcers are more likely to respond to conjunctival resection if not healing with topical steroids, hence surgical intervention is worth considering in the wake of active local inflammation before progressing to systemic medications.
If unilateral, 56% are reported to heal with intensive topical steroids,
If bilateral with non-simultaneous involvement, 50% have shown healing with intensive topical steroids, and
If bilateral ulcers occur simultaneously in both eyes, only 18% have healed with topical steroids alone [15]. Hence, intervention with systemic steroids and immunosuppressive agents may be considered early on in the course of management of such cases. In 86% cases with bilateral PUK, resolution was seen with oral steroids. Role of intravenous pulse steroids has been proven in controlling inflammation in active stage [23].
The presence of active vasculitis demonstrated by biopsy of adjacent conjunctival tissue taken at the time of conjunctival resection would indicate the need for systemic immunosuppression.
Though uncommon in the pediatric population, Mooren’s ulcer requires intensive management [24]. Steroids are the first line of therapy but long-term use of steroids is associated with side effects which need a due consideration from the treating ophthalmologist. Long-term therapy with low potency steroids can be considered in children. Methotrexate is an important immunomodulator that is relatively safe in children and is used as a steroid-sparing agent in those at high risk for steroid associated side effects or for maintenance therapy.
Infectious Ulcerative Keratitis Affecting the Peripheral Cornea [25]
Primarily infective etiology
Targeted anti-microbial treatment based on clinical judgement and culture results following the local protocols for presumed microbial keratitis.
Bacterial infections are treated with either combination therapy with fortified antibiotics following local protocols or monotherapy with fourth-generation fluoroquinolones or even second-generation fluoroquinolones such as ciprofloxacin or ofloxacin depending on local preferred practice patterns. Tuberculosis is managed with standard anti-tubercular treatment, any attendant inflammatory sequelae must be dealt with steroids based on clinical assessment to differentiate the stage of active infection which may worsen with steroids (Fig. 5.1). Syphilis is quite rare, but awareness of its likelihood can help provide early cure (Fig. 5.2). It is usually treated with parenteral penicillin, though erythromycin and doxycycline are also effective against Treponema pallidum. Viral infections could be due to HSV or HVZ and are treated with topical and systemic antivirals such as acyclovir valacyclovir.
Fig. 5.1
a, b Slitlamp microscope (10×) clinical photograph of the Left eye suggestive of sclerokeratouveitis; c Worsening of keratitis with necrotising scleritis seen post steroid use; d Healing noted after treatment for tuberculosis was started in view of underlying Sweet’s syndrome and primary ocular tuberculosis
Fig. 5.2
a Slitlamp microscope (10×) clinical photograph OD suggestive of Peripheral ulcerative keratitis; b Slitlamp microscope (16×) clinical photograph OS suggestive of necrotising scleritis; c OD Healed PUK noted after treatment for underlying treponemal infection was started; d OS Healing noted. Patient was diagnosed to have genital ulcers and a diagnosis of syphilis was confirmed on laboratory tests
Chlamydial infection is treated with oral tetracycline or erythromycin.
Primarily inflammatory etiology with secondary infection
In such situations, one can begin with topical medications to control the infection withholding topical steroids while relying on systemic medications to control the inflammation. Once the local active infection is conquered, one can add topical mild steroids in reduced frequency to reduce the inflammation and promote healing.
General Guidelines for Medical Therapy
Treating Active Disease [26, 27]
The main goal is to control inflammation, halt progression, promote healing of the epithelial defect and repair of damaged stroma, avoid secondary complications, minimize scarring and save or restore vision.
Follow a systematic evidence-based approach.
Institute targeted specific treatment if etiologic agent is known, especially if active infection is present (Table 5.1; Figs. 5.3, 5.4 and 5.5).
Fig. 5.3
Treatment algorithm for presumed infectious Peripheral ulcerative keratitis
Fig. 5.4
Treatment Algorithm in cases of Infectious Peripheral ulcerative keratitis
Fig. 5.5
Treatment Algorithm in cases of suspected infectious etiology (culture negative)
Plan stepwise treatment beginning with topical steroids for inflammatory ulcers combined with surgical measures depending on the response to therapy or extent of disease (Figs. 5.6 and 5.7).
Fig. 5.6
Medical management in cases of inflammatory Peripheral ulcerative keratitis
Fig. 5.7
Treatment algorithm for non-infectious immune-inflammatory peripheral ulcers
Be aware of indications for early institution of systemic immunosuppression with chemotherapeutic agents which could include the following [27–31]: (Fig. 5.8).
PUK with active systemic autoimmune disease particularly potentially lethal vasculitis associated with rheumatoid arthritis, polyarteritis nodosa, Wegener’s granulomatosis, and relapsing polychondritis
PUK with scleritis
PUK with ocular vasculitis detected by conjunctival biopsy
PUK with bilateral simultaneous involvement
PUK with progressive worsening despite aggressive conventional medical and surgical therapy.
Primary Anti-inflammatory Agents as Mainstay of Treatment [10, 27, 29, 32–41]
A step-ladder pattern of approach is important when considering treatment with immunosuppressive agents. The drugs are tapered based on the response seen after 6 months of intensive therapy. Shifting to a less toxic agent is considered in cases when the condition is responding to the treatment and there is adequate control of inflammation [41].
Cyclophosphamide is an important drug used in cases of ulcerative keratitis associated with Rheumatoid and Wegner’s. The commonly used medications with their dosage, frequency, duration, and side effects are summarized in Table 5.2.
Table 5.2
Commonly used medications in the treatment of Peripheral ulcerative keratitis
S. No. | Medications | Mechanism of action | Dose | Frequency | Duration | Side effects |
|---|---|---|---|---|---|---|
1 | Prednisolone | Blocks transcription of anti-inflammatory genes | 1 mg/kg/day | Single dose | Taper over 8–12 weeks [65] | Hyperglycemia, hypertension, osteoporosis, gastric ulcers |
2 | Methotrexate | Antimetabolite which inhibits formation of THFR* thus decreasing DNA synthesis It induces apoptosis of T-Helper cells | 5–25 mg/week | Once a week | Taper as required | Hepatotoxity, low WBC count, ulcerative stomatitis, nausea, fatigue, renal failure |
3 | Cyclophosphamide | Alkylating agent Decreases replication of T-cells | 2 mg/kg/day | Single dose | Taper as required | Bone marrow suppression, nausea, vomiting, stomach aches, haemorrhagic cystitis, diarrhea |
4 | Azathioprine | Purine synthesis inhibitor. It inhibits enzyme required for DNA synthesis, thus affecting proliferating cells
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