Infectious Crystalline Keratopathy (ICK)

72-year-old female with decreased vision

Infectious Crystalline Keratopathy (ICK)

72-year-old female with decreased vision

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Chief Complaint: 72-year-old female with decreased vision referred for "corneal ulcer" in the right eye (OD).

History of Present Illness: The patient is a monocular female who was referred for evaluation and treatment of a corneal ulcer in her right eye.

Past Ocular History: Extensive prior ocular issues, including primary open angle glaucoma, neurotrophic keratitis OD, and multiple bouts of herpes simplex virus (HSV) keratitis in both eyes (OU). Surgically, she had undergone cataract extraction in both eyes (posterior chamber intraocular lens implant in the right eye and aphakic in the left eye) and penetrating keratoplasty in the right eye in 1996. She underwent three penetrating keratoplasties in the left eye (OS) in 1997, 1998 and 2000, and eventually required an evisceration for a blind, painful eye in 2003.

Medical History: Significant for diabetes mellitus, hypertension, hypothyroidism, asthma, gastroesophageal reflux disease, hiatal hernia, osteoporosis, syncope, elevated cholesterol, skin dermoids and a history of myocardial infarction status post coronary artery bypass grafting x 4 vessels.

Medications (OD only): brimonidine P 0.15% BID, latanoprost 0.005% QHS, and sodium chloride 5% QID and valacyclovir by mouth, 500mg BID. The referring doctor had recently placed her on hourly moxifloxacin drops.

Family History: Noncontributory

Social History: No alcohol use. Quit smoking in 1980’s.

Ocular Exam:

• Visual Acuity, with best correction:
  • Right eye (OD) -- Count Fingers at 1 foot
  • Left eye (OS) -- NLP (prosthesis)
• Intra-ocular pressure, OD: 18
• Pupil, OD: 3mm in light, 2mm in dark. Round and reactive to light
• Confrontation Visual Field, OD: Full to hand motions
• Pachymetry, OD: 688 microns
• External and anterior segment examination:
  • OD -- epithelial defect (2.6mm vertically by 2.8mm horizontally) centrally in corneal graft. White, arborizing, crystalline infiltrate present in anterior 1/3 of corneal stroma under epithelial defect (see Figure 1). Inferior punctual plug in place. There was a rare cell per high power field view in the anterior chamber. Thin, white, mucoid discharge.
  • OS -- Prosthesis, no discharge
• Dilated fundus exam (DFE), OD: No view

Figure 1

1A: Crystalline infiltrate centrally in corneal graft, OD.	1B: Magnified view of crystalline pattern, OD.

Course: The patient was admitted to the hospital, placed on vancomycin (25mg/ml) drops Q1 hour, moxifloxacin drops Q1 hour, valacyclovir 1000mg po BID and monitored closely. The epithelial defect continued to enlarge over the next 2 days of inpatient treatment with no improvement. The antibiotics were tapered to q2h because of concern with toxicity and bandage contact lens was applied to the surface of the cornea. The epithelial defect slowly healed over the next several days, but the infiltrates persisted. The patient ultimately required a repeat penetrating corneal transplant. The patient was seen in follow-up three weeks prior to this publication. The new graft remained clear with no evidence of recurrent infection.

Discussion: Infectious crystalline keratopathy (ICK) was first described in the 1980's as a unique and distinctive clinical entity characterized by white, branching, crystalline, opacities within the corneal stroma and little or no associated inflammatory response (Gorovoy MS 1983, Dunn S 1985, and Meisler DM 1984). A sharply demarcated, snowflake-like stromal opacity on a background of clear, uninflammed corneal graft is the classic presentation (see Figure 1B), though variations on this theme are common.

Though ICK is most commonly associated with Streptococcus species (α-hemolytic Streptococcus is the most common cause), the clinical entity described above may be caused by a variety of organisms. There are case reports of clinical ICK from culture-proven S. pneumoniae, Haemophilus species, Peptostreptococcus, Pseudomonas aeruginosa, G. Haemolysans as well Candida and Alternaria fungi. In this case, culture of corneal scrapings revealed heavy growth of Group G, β-hemolytic Streptococcus.

ICK occurs more commonly in corneal grafts or otherwise immunocompromised corneas. The most common risk factors for infectious crystalline keratopathy include history of penetrating keratoplasy (usually many months after transplant), corticosteroid use, and contact lens wear. It is likely that gram-positive cocci from the periocular skin or conjunctiva gain access to the stroma by tracking along suture lines or through micro-defects in the corneal epithelium. As opposed to many other bacterial infections of the cornea, the epithelium in IKC may appear intact and there is a paucity of inflammatory infiltrate. Some have suggested that the bacterial colonies that cause ICK are less pathogenic, allowing them to invade and replicate within the stroma without inciting much response in the host.

Though classic ICK is very distinctive, proper organism identification still requires isolation of the offending organism by deep corneal scrapings or corneal biopsy (Khater, 1997). Histopathology of corneal biopsy or corneal buttons may reveal pockets of bacteria (usually Gram positive cocci) between intact lamellae of corneal stroma with a paucity of inflammatory infiltrate.

Treatment initially consists of cessation (or at least strict minimization) of topical steroids and prolonged use of topical bactericidal antibiotics. We recommend starting with vancomycin or other potent antibiotic with good gram-positive coverage and adapting medications depending on culture or biopsy results. Some authors suggest systemic antibiotics (including methicillin and penicillin) in severe cases. However, ICK is notoriously difficult to treat, demonstrating poor and slow response to medications. Debilitating stromal scars or recurrence of infection are common. In many cases, despite appropriate antimicrobial therapy, repeat penetrating keratoplasty or lamellar keratectomy may be required.

Diagnosis: Infectious Crystalline Keratopathy (ICK)

EPIDEMIOLOGY No described racial or gender predisposition Found in corneal grafts and otherwise immunocompromised corneas (usually 3-36 months after transplant) Almost always Streptococcus species (especially α-hemolytic streptococcus viridans)	SIGNS Exam: needle-like crystalline pattern with a snowflake or ice crystal appearance of white opacities within the corneal stroma minimal or no surrounding inflammation may be conjunctival injection or chemosis with or without epithelial defect Histopathology: biopsy or transplant specimen pockets of gram-positive bacteria between corneal lamellae with a paucity of inflammatory cells
SYMPTOMS Variable symptoms including pain, reduced vision, injection, and photophobia	TREATMENT Topical therapy with Vancomycin (25mg/ml) Q1hr adjust depending on culture results (not all ICK is gram positive bacteria) Systemic antibiotic in severe cases (IV methicillin or penicillin) Hold immunosuppresion drops if possible May require treatment for many weeks or months Repeat corneal transplant or lamellar keratectomy may be required

Differential Diagnosis:

• Fungal keratitis
• Bacterial keratitis
• Herpes simplex keratitis
• Non-infectious crystalline keratopathy
  • including Schnyder's crystalline dystrophy, tyrosinemia, gout, multiple myeloma, monoclonal gammopathy, Waldenstrom's macroblulinemia, etc.
• Graft rejection