Cornea 19(4): 455–458, 2000. © 2000 Lippincott Williams & Wilkins, Inc., Philadelphia

Infectious in Climatic Droplet Keratopathy

M.S. Sridhar, M.D., Prashant Garg, M.S., Sujatha Das, M.S., Geeta Vemuganti, M.D., Usha Gopinathan, M.Sc., and Gullapalli N. Rao, M.D.

Purpose. To report the ulcer characteristics, microbiologic data, most important predisposing factor for infectious keratitis in South and outcome of infectious keratitis associated with climatic droplet Africa. In this study, we present our experience of infectious kera- keratopathy (CDK), suggesting that CDK is a predisposing factor titis in patients with CDK. for infectious keratitis. Methods. Medical records of 32 patients (34 eyes) in whom infectious keratitis was seen in association with CDK were retrospectively reviewed. Data were collected regard- MATERIALS AND METHODS ing the nature of CDK lesions, infiltrate characteristics, organisms isolated, and outcome. Results. CDK was peripheral in 16 (47.1%) A retrospective analysis of medical and microbiology records of eyes, central in 8 (23.5%), and diffuse in 10 (29.4%). The CDK all cases of infectious keratitis with associated CDK seen in the lesions were nodular and elevated in all eyes. The infiltrate was Service, L.V. Prasad Eye Institute—a tertiary eye care adjacent to the CDK lesions in 28 eyes (82.4%). The infiltrate size centre at Hyderabad, India—was done. Data collected included (widest dimension) ranged 2–6 mm in 18 eyes (52.9%) and was >6 age and sex of the patient, presenting symptoms, any other local or mm in 7 (20.5%). The infiltrate was full thickness in 15 eyes systemic predisposing factors for , nature of CDK (44.1%) and was involving up to the middle third of the corneal lesions, and involvement of the other eye. Ulcer characteristics, stroma in another 18 (52.8%). was seen in all. Bacteria were commonly isolated. Staphylococcus epidermidis (six eyes) including the site of the infiltrate in relation to CDK lesions, size and Streptococcus pneumoniae (five eyes) were the common bac- of the infiltrate, depth of the infiltrate, presence, and—if present— teria isolated. Resolution with medical treatment was seen in 20 size of the hypopyon and presence of secondary , were (58.8%) eyes. Conclusions. CDK is a predisposing factor for in- noted in all patients. All patients had undergone corneal scraping fectious keratitis. Treatment should be considered for advanced under topical anesthesia using the No. 15 surgical blade for mi- and nodular lesions, even if they are peripheral, to prevent infec- crobiologic investigations. Smears were prepared for Gram stain, tious keratitis. Giemsa stain, and potassium hydroxide preparation. Sheep blood Key Words: Climatic droplet keratopathy—Infectious keratitis— agar, sheep blood chocolate agar, brain heart infusion broth, thio- Bacteria—Predisposing factors. glycolate broth (supplemented with vitamin K and hemin), Sab- ouraud’s dextrose agar, and nonnutrient agar with live Escherichia coli overlay for Acanthamoeba were inoculated. Although all other media were incubated at 35°C for 7 days, Sabouraud’s dextrose Climatic droplet keratopathy (CDK) is a degenerative condition agar was incubated at 27°C for 7–14 days. Growth on culture characterized by accumulation of translucent material in the su- media was identified using standard microbiologic procedures. Ini- perficial corneal stroma within the interpalpebral area. Progressive tial treatment was based on smear results. Therapy was modified in 1 accumulation can lead to significant visual disability. This entity cases not responding to initial medical therapy based on the sen- has been reported from widely separated geographic areas and, in sitivity pattern of growth. The end result and the final visual acuity its extreme form, is seen in some regions like the Dahlak Islands were analyzed. of the Red Sea, Somalia, and India.1–3 Reported etiologic factors are radiation and microtrauma, including sand, dust, wind, and drying.4–7 Apart from , CDK may RESULTS predispose to secondary infections of the cornea. Ormerod8 re- We studied 34 eyes of 32 patients (28 men and 4 women) who ported CDK as the third most prevalent factor predisposing to had infectious keratitis in association with CDK. Of these, 30 microbial keratitis in the developing world. belonged to lower socioeconomic status and 2 to higher socioeco- Similarly, Carmichael et al.9 identified this to be the second nomic status. The age of the patients ranged 30–80 years. Two patients had involvement of both eyes. Pain, redness, and de- Submitted November 6, 1999. Revision received February 28, 2000. creased vision were the presenting symptoms in all patients. Two Accepted March 4, 2000. (5.9%) patients had diabetes mellitus and four (11.8%) were on From the Cornea Centre (M.S.S., P.G., S.D., G.N.R.), the Pathology topical corticosteroids before the onset of symptoms. The CDK Centre (G.V.), and the Jhaveri Microbiology Centre (U.G.), L.V. Prasad lesions were central in 8 (23.5%), diffuse in 10 (29.4%), and Eye Institute, Hyderabad, India. Address correspondence and reprint requests to Dr. M.S. Sridhar, Con- peripheral in 16 (47.1%) eyes. CDK lesions were seen in the other sultant, Cornea Services, L.V. Prasad Eye Institute, L.V. Prasad Marg, eye in 20 patients (58.8%). Banjara Hills, Hyderabad - 500 034, India. E-mail: [email protected] The deposits were nodular and elevated in all cases. The infil-

455 456 M.S. SRIDHAR ET AL.

TABLE 1. Organisms isolated from 34 eyes

Organism isolated Frequency (n) Staphylococcus epidermidis 6 Streptococcus pneumonia 5 a´ Hemolytic streptococcus 3 Staphylococcus aureus 1 Pseudomonas aeroginosa 2 Corynebacterium 2 Acinetobacter 1 Aspergillus flavus 1 Fusarium solani 1 Curvularia 1 Unidentified hyaline 1 No organisms 14

gus was isolated in four (Fig. 4). One case had a mixed bacterial and fungal infection and in three cases, two bacteria were isolated. FIG. 1. Slit view of a case of CDK showing full thinkness infiltrate Initially, all of these cases were managed as inpatients and, adjacent to CDK with surrounding corneal edema and Descemet’s when ulcer showed signs of resolution, they were managed as folds. outpatients. The initial topical treatment was started with 0.3% ciprofloxacin eye drops in 21 eyes, a combination of fortified trate was adjacent to CDK lesions in 28 (82.4%) eyes (Fig. 1) and cefazolin (5%) and fortified gentamicin (1.4%) in 9, and 5% na- was away from the lesion in 6 (17.6%). In the former group, two tamycin eye drops in 4. The initial frequency of these medications had significant , one had a positive history of trauma, was every half hour. In four cases of bacterial ulcers that were not and was seen in two. In the later group, one had a responding to initial treatment, therapy was modified based on a positive history of trauma and another had lagophthalmos. In the sensitivity pattern. The infiltrate resolved with medical treatment remaining four cases, no other predisposing factor could be iden- forming a scar in 20 (58.8%) eyes (Fig. 5). Table 2 lists the tified. outcome in all cases. The outcome data were available for 26 eyes. The infiltrate size was <2 mm in 9 (26.4%), was between 2–6 Five patients underwent therapeutic penetrating keratoplasty. The mm in 18 (52.9%), and was >6 mm in 7 (20.5%) eyes (Fig. 2). The indications for keratoplasty were progressive extension of infiltrate infiltrate was involving the full thickness of cornea in 15 (44.1%) in spite of medical treatment threatening the limbus in one and cases. It was restricted to the anterior one-third in nine (26.4%) and rapid progression with perforation in rest of the cases. Two eyes up to the middle one-third in another nine (26.4%). Hypopyon was were eviscerated. One case presenting as a large infiltrate that later seen in all patients and was <2 mm in 31 (91.2%) eyes. perforated—causing sloughing of whole cornea—was eviscerated. Smears were positive for microorganisms in 21 (61.7%) eyes. Another perforated corneal ulcer with limbus-to-limbus involve- Gram-positive cocci were seen in 14, and Gram-negative bacilli ment with associated was also eviscerated. There were seen in one, both Gram-positive cocci and Gram-negative was an improvement in visual acuity in 19 eyes. bacilli in two, and fungus in four. Culture revealed a significant growth of microorganisms from 22 eyes. The various organisms DISCUSSION isolated are shown in Table 1. Bacteria were commonly isolated (Fig. 3). Staphylococcus epidermidis (six eyes) and Streptococcus CDK is a slowly evolving corneal degeneration related to cu- pneumoniae (five eyes) were the common bacteria isolated. Fun- mulative climatic exposure.10 Bietti et al.11 described this corneal

FIG. 2. A case of bacterial keratitis (Corynebacterium) with large FIG. 3. A case of bacterial keratitis (Pseudomonas aeruginosa) with infiltrate. large infiltrate adjacent to CDK.

Cornea, Vol. 19, No. 4, 2000 INFECTIOUS KERATITIS IN CDK 457

TABLE 2. Outcome in 34 eyes

Frequency n% Corneal scar 20 58.8 Therapeutic penetrating keratoplasty-clear graft 2 5.9 Therapeutic penetrating keratoplasty-failed graft 2 5.9 Evisceration 2 5.9 Lost to follow-up 8 23.5

positively for fibrin. Patients are asymptomatic unless the disease is advanced to the point of decreased vision. Superficial keratec- tomy, lamellar or penetrating keratoplasty, and excimer laser pho- totherapeutic keratectomy are various surgical options that have FIG. 4. A case of (Curvularia lunata) with infiltrate been tried in the management of CDK involving the visual axis adjacent to CDK lesions with a large hypopyon. and impairing the vision.1,13 Freedman14 classified this entity to five stages. Stage 1, which condition occurring in the male population of the Persian gulf and was the earliest form of the condition, is characterized by small oil Red Sea area in 1955. Freedman12 noticed similar changes among droplets seen in the lower half of the cornea and occurring near the the Inuit (Eskimo), Indian, and white settlers living along the limbus and stage 5 is characterized by ulceration and infection. coastline of Labrador and Northern Newfoundland. Since then, it Ormerod et al.10 reported the serious occurrence in the natural has become increasingly apparent that this destructive degenera- history of advanced CDK. According to their experience, infection tive condition occurs in many different parts of the world and has of the devitalized corneal deposits of severe climatic keratopathy is been named with various terminologies. common with an unremarkable microbial etiologic spectrum. The CDK has been classified into three basic types. Type 1 occurs areas of densest plaque or nodular formation were invariably in- bilaterally in the cornea without evidence of other ocular pathol- volved. There was rapid dissolution of the keratopathy material so ogy. Type 2, or secondary spheroidal degeneration, occurs in the that the microbial keratitis became horizontally oval. Rapid pro- cornea in association with other ocular pathology. Type 3 is the gression of infection, high prevalence of hypopyon, and late per- conjunctival form of the degeneration, which may occur concur- foration were noted. rently with types 1 or 2.5 CDK presents clinically as clear to Bacterial infections commonly due to Staphylococci or Strep- yellow-gold spherules seen in the subepithelium, within Bow- tococci can complicate a corneal epithelial erosion associated with man’s membrane or in the superficial corneal stroma. They may CDK.15 Ormerod8 reported the causation and management of mi- measure 0.1–0.4 mm.4 Histologically, the deposits appear as ho- crobial keratitis in subtropical Africa. CDK was found to be the mogenous globular deposits of variable size located in the super- local ocular predisposing factor for microbial keratitis in 10 cases ficial corneal stroma and subepithelial space. The deposits disrupt (third most prevalent cause). The organisms isolated were coagu- the Bowman’s membrane and, when advanced, can elevate and lase negative Staphylococci in three, Streptococcus pneumoniae in thin the corneal epithelium. Histochemical analysis demonstrates two, Pseudomonas aeruginosa in one, Proteus mirabilis in one, extracellular deposition of a complex of proteins including tryp- Klebsiella spp in one, Corynebacterium in one, and Aureoha- tophan, cystine, cysteine, and tyrosine.1 The deposits also stain sidium pululans (yeast) in one. Carmichael et al.9 reported corneal ulceration at an urban African hospital. In 283 corneal ulcers from 274 patients, CDK was the second most common local predispos- ing factor for corneal ulcers. It was the cause in eight of the central bacterial ulcers and two cases of fungal ulcers (phoma cupyrena and Curvularia lunata). In these ulcers, the nodular form of CDK, which flakes off leaving an area of denuded epithelium, was noted. Though CDK has been identified as a predisposing factor for in- fectious keratitis, a series of infectious keratitis in association with CDK is not reported so far. In this series, in 27 eyes no local predisposing factor for infec- tious keratitis other than the fact that CDK was found. Four pa- tients were on topical corticosteroids before the development of infectious keratitis. The infiltrate was adjacent to the lesion in majority of the patients. In half of the cases, the infiltrate measured 2–6 mm. The infiltrate was full thickness in nearly half of the patients. All were associated with hypopyon. Bacteria were com- monly isolated; Staphylococcus epidermidis and Streptococcus FIG. 5. Clinical picture of the patient in Figure 3 after treatment pneumoniae were the bacteria most commonly isolated. The infil- showing corneal scar (arrow) with CDK lesions (arrow head). trate resolved with medical treatment in the majority of patients.

Cornea, Vol. 19, No. 4, 2000 458 M.S. SRIDHAR ET AL.

Advanced lesions are known to be nodular and may break 6. Klinworth GK. Chronic actinic keratopathy: a condition associated through the epithelium, predisposing to corneal ulcer. Dissolution with conjunctival elastosis () and typified by characteristic of keratopathy and infection of devitalized epithelium has been extracellular concretions. Am J Pathol 1972;67:327–48. reported before.15 Tear film breakup at the site of the elevated 7. Taylor HR, West SK, Rosenthal FS, Munoz B, Newland HS, Emmett EA. Corneal changes associated with chronic UV irradiation. Arch lesions leading to desiccation of the surrounding epithelium may Ophthalmol 1989;107:1481–4. be a contributing factor to the development of infectious keratitis. 8. Ormerod LD. Causation and management of microbial keratitis in In conclusion, CDK is a predisposing factor for infectious kera- subtropical Africa. 1987;94:1662–8. titis. In addition to decreased vision, treatment should be consid- 9. Carmichael TR, Wolpert M, Koornnof HJ. Corneal ulceration at an ered for advanced and nodular lesions even if they are peripheral urban African hospital. Br J Ophthalmol 1985;69:920–6. for the prevention of infectious keratitis. 10. Ormerod DL, Dahan E, Hagele JE, Guzek JP. Serious occurrences in the natural history of advanced climatic keratopathy. Ophthalmology 1994;101:448–53. REFERENCES 11. Bietti GB, Guerra P, Ferraris de Gaspare PF. La dystrophie corncene nodulaire en ceinture des pay tropicanx. Bull Soc Fr Ophthalmology 1. Gray RH, Johnson GJ, Freedman A. Climatic droplet keratopathy. 1955;68:101–29. Surv Ophthalmol 1992;36:241–53. 12. Freedman A. Labrador keratopathy. Arch Ophthalmol 1965;74:198– 2. Rodger FC. Clinical findings, course and progress of Bietti’s corneal 202. Br J Ophthalmol degeneration in the Dahlak islands. 1973;57:657–64. 13. Badr IA, al Rajhl A, Wagoner MD, Dunham T, Teichmann KD, Cam- 3. Johnson G, Minassain D, Franken S. Alterations of the anterior eron JA. Phototherapeutic keratectomy for climatic droplet keratopa- Br J Ophthalmol capsule associated with climatic keratopathy. 1989; thy. KKESH Excimer laser study group. King Khaled Eye Specialist 73:229–34. Hospital. J Refract Surg 1996;12:114–22. 4. Goodfriend AN, Ching SST. Corneal and conjunctival degenerations. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea. Vol. II. St. 14. Freedman J. Band shaped nodular dystropy of the cornea in Bantu Louis: Mosby, 1997:1119–37. speaking negroes of South Africa. Arch Ophthalmol 1973;1:149–55. 5. Fraunfelder FT, Hanna C. Spheroidal degeneration of the cornea and 15. Wilhelmus KR. Bacterial keratitis In: Pepose JS, Holland GN, Wilhel- : clinical course and characteristics. Am J Ophthalmol mus KR, eds. Ocular infection and immunity. St. Louis: Mosby, 1972;74:821–8. 1996:978–1031.

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