CORNEA/OCULAR SURFACE DISEASE
From the 7th Annual Downeast Ophthalmology Symposium, presented by the Maine Society of Eye Physicians and
Surgeons
Educational Objectives
The goal of this program is to improve the care of patients with corneal and ocular surface disease. After hearing and
assimilating this program, the clinician will be better able to:
 | 1. Identify ophthalmologic conditions that may be managed effectively through minor surgical procedures.
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| 2. Safely and effectively perform minor surgical procedures for ocular disease.
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| 3. Describe common indications for excimer laser phototherapeutic keratectomy (PTK).
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| 4. Identify potential complications of PTK.
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| 5. Describe evidence-based strategies for managing herpes simplex viral keratitis.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee
to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary
business or commercial interest. For this program, the following has been disclosed: Dr. Rapuano has been a consultant to Allergan
and on the lecture boards for Allergan, Alcon, and Inspire. The planning committee reported nothing to disclose.
Acknowledgments
Dr. Rapuano was recorded at the 7th Annual Downeast Ophthalmology Symposium, presented September 19-21, 2008,
in Bar Harbor, ME, by the Maine Society of Eye Physicians and Surgeons. The Audio-Digest Foundation thanks Dr.
Rapuano and the Maine Society of Eye Physicians and Surgeons for their cooperation in the production of this program.
Christopher J. Rapuano, MD
Professor of Ophthalmology and Co-Director, Cornea Service and Refractive Surgery Department, Wills Eye Institute,
Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA
Office and Minor Surgical Management of Ocular Surface Diseases
| Molluscum contagiosum: treatment options—shave or excisional biopsy; cautery; cryotherapy; on eyelid margin,
speaker prefers curettage—easy, safe, and effective; typically performed without anesthesia; use small chalazion scoop,
#15 or #11 blade, or jeweler’s forceps to core central umbilication (enough to cause bleeding); lesion may take several
weeks to resolve (4-6 wk for follicular conjunctivitis)
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| Vernal keratoconjunctivitis
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| Treatment: topical therapy first line; allergy medications, steroids, and cyclosporine; for shield ulcer or epithelial defect,
antibiotics
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| Shield ulcer: diagnosis—well-delineated gray or cream-colored infiltrates in superficial cornea; may be white and fibrotic;
may have calcified appearance (these often do not respond well to medical treatment); treatment of fibrotic
shield ulcer—aggressive scraping with #15 blade; remove calcified fibrotic superficial tissue to Bowman’s membrane
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| Superior limbic keratoconjunctivitis (SLK): diagnostic pearl—flip eyelids to detect floppiness; medical
therapy—lubricants, steroids, mast cell stabilizers, and cyclosporine; recent report that cyclosporine (Restasis) worked well
for SLK (speaker has had mixed results); if medical therapy ineffective, next step surgery—punctal plugs or cautery
(many patients respond well to lubrication); silver nitrate solution used in past (not silver nitrate stick); speaker’s preferred
treatment conjunctival cautery—if cautery ineffective, consider conjunctival resection or recession and/or amniotic membrane
transplantation [AMT]); procedure performed with topical anesthesia; balloon out superior conjunctiva and apply, eg,
local lidocaine; apply hand-held hotpoint cautery to large area of conjunctiva (thermal burn tightens conjunctiva); effect
more localized than silver nitrate; not painful; with healing, minimal scarring and significant symptom improvement; retreatment
may be indicated
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| Severe dry eye: medical therapy—lubricants; cyclosporine; secretagogues; autologous serum; surgical—punctal plugs
(if ineffective, punctal cautery works well in many patients); small lateral tarsorrhaphy; punctal cautery—generous application
of local anesthesia key; 0.5 to 1.0 mL lidocaine per punctum; use high-temperature cautery probe; bend tip to
penetrate 3 to 4 mm into punctum; apply heat until punctum “sizzles”
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| Overview: anterior basement membrane (ABM) or other corneal dystrophies—diffuse epithelial pathology; posttraumatic
lesions—localized and unilateral
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| Medical treatment: lubrication; bandage soft contact lens (BSCL); dextran (Dehydrex) to dehydrate cornea (under investigation
by Food and Drug Administration [FDA])
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| Surgical treatment
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| Posttraumatic localized lesions outside visual axis: anterior stromal puncture; use 25-gauge needle at 10% to 20% stromal
depth; performed through intact epithelium or epithelial defect
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| ABM or diffuse pathology: epithelial debridement; excimer laser phototherapeutic keratectomy (PTK); diamond bur
polishing of Bowman’s membrane—works well and can be performed in office; debride all loose epithelium with
Kimura spatula, Weck-Cel sponge, or #15 blade; use large-diameter corneal diamond bur (5-mm tip) to smooth
Bowman’s membrane; treat uniformly (surgically induced irregular astigmatism is concern)
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| Chronic epithelial defect
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| Causes: neurotrophic causes; exposure
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| Medical treatment: lubricants; antibiotics; pressure patching; cyclosporine; BSCL
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| Surgical treatment
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| Lateral tarsorrhaphy: tools include glue, botulinum toxin type A [Botox], and suture; suture tarsorrhaphy fast and effective
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| Amniotic membrane graft: using suture or fibrin glue—place AMT tissue onto surface of cornea with basement membrane
side up so that epithelium grows over it; Prokera—AMT tissue secured to polymethyl methacrylate (PMMA)
ring placed stromal side down; expensive (≈$1000); remarkably well tolerated; after 1 to 3 wk, AMT tissue dissolves
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| Band keratopathy: diagnosis—gray-white calcium deposit in superficial cornea; may be thin and uniform or large and
flaky; if patient symptomatic, consider ethylenediaminetetraacetic acid (EDTA) chelation—efficacy superior to PTK;
topical anesthesia at slit lamp; remove epithelium with #15 blade (if epithelium not removed, EDTA will not dissolve calcium);
apply dilute EDTA on Weck-Cel sponge or cotton-tipped applicator until calcium dissolved (10-45 min)
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| Partial limbal stem cell abnormalities
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| Causes: previous surgery (eg, glaucoma surgery involving mitomycin-C [MMC] or 5-fluorouracil [FU]); long-term contact
lens wear
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| Treatment
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| Medical: lubrication; contact lens
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| Surgical: for large or total limbal stem cell abnormality, limbal stem cell transplantation; selective epithelial
debridement—performed at slit lamp, with topical anesthesia; with blade, remove abnormal epithelium to limbus;
consider BSCL or pressure patch to allow normal epithelium to grow in from below; may require second or third
partial epithelial debridement; treatment can be repeated years later with good effect; patients symptomatic when epithelium
crosses visual axis
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Excimer Laser Phototherapeutic Keratectomy
| PTK indications: anterior corneal pathology affecting visual function—eg, superficial dystrophies, superficial scars,
elevated lesions (not deep scars); superficial granular dystrophies; keratoconus nodule (elevated lesion); Reis-Bucklers
dystrophy; recurrent dystrophies
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| Overview: goal to clear central cornea of opacity; masking agents can be effective aid in achieving smooth surface; do
not flatten cornea (ablate and check frequently); masking agent fills in “valleys” and excimer laser ablates and smooths
out “mountain tops” to achieve smoother surface
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| Smooth central stromal opacity: lattice, granular, or Reis-Buckler dystrophy; use large-diameter ablation (≤6.5 mm); set
ablation depth into stroma to two-thirds or three-fourths of intended final depth, then check it at slit lamp (concern that
too much tissue removed); epithelium acts as smoothing agent; check at slit lamp and reablate as necessary; remove
bulk of pathology (crystal clarity not goal; reablation always possible); do not ablate deep opacities; irrigate with 30
mL of saline; macular dystrophy is full-thickness corneal abnormality (not best indication for PTK)
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| Rough elevated lesions: remove epithelium from high points (fill in low points with masking agent, then chip away elevated
lesions); start with small diameter ablation zone (eg, 0.6 mm); then use larger zone to smooth entire central surface;
ablate and check frequently
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| Recurrent erosions with ABM dystrophy: remove epithelium from involved area (set ablation zone to cover entire area);
ablate 5 or 6 µm of Bowman’s membrane
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| PTK complications: poor epithelial healing; corneal infection or ulceration; corneal haze or scar; decreased best-corrected
visual acuity (BCVA); induced hyperopia (induced myopia less common); induced irregular astigmatism; recurrence
of dystrophy or Salzmann’s nodular degeneration (warn patients that procedure does not cure granular dystrophy);
recurrence of herpes simplex virus (HSV) keratitis
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| PTK results: Rapuano, 1997—28 eyes with corneal opacities; reepithelialization at mean of 4 days (range 2-11 days);
preoperative goal achieved in 79% of patients (no change in 18%; 1 patient worse due to induced irregular astigmatism);
PTK for keratoconus nodules (Rapuano)—15 eyes (all contact lens-intolerant); goal to return to contact lens wear (not
to treat keratoconus); results—11 patients refit with rigid gas permeable (RGP) lenses; 4 tolerated spectacles; 3 nodules
recurred (1 retreated and clear years later); overall, results good; some patients have not had recurrence since early 1990s;
summary—many papers show that PTK effective for anterior corneal pathology; anterior stromal lesions respond well,
but deeper ablations tend to cause more hyperopia; elevated lesions and recurrent erosions also respond well, but can often
be treated by other means (eg, superficial keratectomy with blade); laser versatile and can achieve good results
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| PTK with topical MMC: Marcon and Rapuano, 2002—case report of repeat PTK and MMC for recurrent Salzmann’s
nodular degeneration after PTK; result—no recurrence at 1 yr; Ayres and Rapuano, 2005—13 eyes treated for
anterior corneal disease; PTK performed with subsequent administration of MMC (0.02% for 2 min [speaker uses 1
min]); results—mean time to epithelial healing <3 days; no corneal or scleral melting or scarring; minimal postoperative
PTK haze; minimal or no recurrence of disease at 1 to 2 yr; treatment delays but does not prevent recurrences
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| PTK and ultrasonographic biomicroscopy (UBM; Rapuano, 2003): 20 eyes with anterior stromal dystrophy;
results—mean uncorrected visual acuity (UCVA) and BCVA improved; UBM measurement of pathology not correlated
with depth of treatment required during PTK
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| Newer indications for PTK: treatment of fungal keratitis (Lin, 2005); laser in situ keratomileusis (LASIK) flap striae
(Steinert, 2004); LASIK flap complications (Muller, 2005; Weisenthal, 2003); PRK complications (Vinciguerra, 2005);
painful bullous keratopathy in developing world (Sharma, 2008)
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| Conclusions: PTK can work well to improve functional vision; patient selection and counseling to establish reasonable
expectations critical; slit lamp examination and pachymetry important in preoperative evaluation; MMC 0.02% for 1 min
safe and effective
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| Best indications for PTK: superficial, smooth anterior corneal pathology; central elevated lesions not treatable with
blade; recurrent erosions with ABM dystrophy (remove 5-6 µm); PTK versatile (indications evolving)
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Managing HSV Keratitis: The Herpetic Eye Disease Study (HEDS) and Beyond
| Acyclovir for HSV stromal keratitis (Barron, 1994): 104 patients treated with oral acyclovir (400 mg 5 times/
day), or placebo, to decrease inflammation; all received 10-wk course of topical steroid and trifluridine (Viroptic) with
taper; results—no statistically significant benefit seen with oral acyclovir for active HSV stromal keratitis; however,
some benefit seen in small subset of patients with necrotizing HSV keratitis
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| Topical steroids for HSV stromal keratitis (Wilhelmus, 1994): 106 patients given 10-wk taper of topical steroids
or placebo to decrease inflammation; all patients received trifluridine; patients who worsened on placebo removed
from trial and treated; results—topical steroids significantly decreased stromal inflammation and shortened duration of
stromal keratitis; however, vision at 6 mo same in both groups; conclusion—topical steroids with trifluridine should be
used for HSV stromal keratitis, but not critical that topical steroids be started immediately
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| Oral acyclovir for HSV iridocyclitis (HEDS Group, 1996): 50 patients received 10 wk of oral acyclovir (400
mg 5 times/day) or placebo; all patients received topical steroids and trifluridine; results—improvement on oral acyclovir
not statistically significant, compared to placebo; speaker’s view—use full-dose oral acyclovir in patients with significant
HSV iridocyclitis; taper to 400 mg 2 times/day or discontinue, using concomitant steroids and trifluridine
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| HSV epithelial keratitis trial (HEDS Group, 1997): 287 patients with keratitis <1 wk received 3-wk course of
acyclovir or placebo to decrease risk for future stromal keratitis and/or iritis; all patients received trifluridine; results—
no difference between groups in development of stromal keratitis or iritis over next 12 mo; rates of stromal keratitis and
iritis increased in patients with previous history; conclusion—do not use short course of acyclovir to prevent stromal
keratitis or iritis in patients with epithelial keratitis
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| Acyclovir to prevent recurrent HSV (HEDS Group, 1998): 703 patients with history of HSV eye disease over
previous 12 mo (inactive and untreated ≥1 mo); patients received oral acyclovir 400 mg or placebo bid for 1 yr (patients
followed additional 6 mo); results—during year of treatment, rate of recurrent ocular HSV disease 19% in acyclovir
group (32% in placebo group); rate of recurrence of stromal keratitis 14% in acyclovir group (28% in placebo
group); orofacial herpes (recurrence rate 19% in acyclovir group; 36% in placebo group); no rebound in rate of HSV
disease 6 mo after acyclovir discontinued; conclusion—long-term acyclovir 400 mg bid significantly reduced risk for
recurrent HSV ocular disease
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| Case 1: first episode of HSV dendrite; options—1) trifluridine drops 8 or 9 times/day for 1 wk, then taper; 2) acyclovir
400 mg 5 times/day for 1 or 2 wk; 3) both regimens combined; speaker’s choice—each approach reasonable; consider
full-dose trifluridine 8 or 9 times/day for 1 wk, then 4 times/day for 1 wk, then stop; follow for 4 to 7 days after, depending
on severity
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| Case 2: fourth episode of dendrite, minimal scarring, vision still good; options—trifluridine, acyclovir, or both;
speaker’s choice—combination therapy; discontinue topical trifluridine in 1 to 2 wk, taper acyclovir to 400 mg bid for
long-term prophylaxis
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| Case 3: first episode of HSV stromal keratitis; mild edema, no corneal scarring, vision 20/40; options—follow patient off
medications; trifluridine drops; steroid drops; acyclovir pills; combination therapy; speaker’s choice—follow patient off
medications; if not improving over few weeks, prescribe steroids with antiviral coverage
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| Case 4: fourth episode of stromal keratitis; vision 20/50; mild-to-moderate edema and patchy scarring; patient not on any
medications; same treatment options as case 3; speaker’s choice—topical steroid with acyclovir (400 mg bid); taper steroids
slowly to avoid recurrence and continue acyclovir
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| Case 5: significant iritis and history of HSV dendrite years ago; speaker’s choice—steroids, cycloplegia and acyclovir
(full dose, 5 times/day) until improved (≈2 wk), then taper topical steroids slowly and taper oral acyclovir to bid dosing
for 6 to 12 mo or longer
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| Case 6: patient with history of HSV presents with severe scarring, lipid, and neovascularization; speaker’s choice—oral
acyclovir 400 mg bid for years
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| Summary: treat HSV dendrites with topical antiviral medication or full-dose oral antivirals for 10 to 14 days; iritis
treated with topical steroid and full-dose oral antivirals until patient improved; history of multiple HSV episodes treated
with prophylactic antivirals for months to years to reduce recurrences; steroids tapered slowly
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Suggested Reading
[No authors listed]: A controlled trial of oral acyclovir for iridocyclitis caused by herpes simplex virus. The Herpetic Eye
Disease Study. Arch Ophthalmol 115:703, 1997; [No authors listed]: Acyclovir for the prevention of recurrent herpes simplex
virus eye disease. Herpetic Eye Disease Study Group. N Engl J Med 339:300, 1998; Ayres BD et al: Phototherapeutic
keratectomy with intraoperative mitomycin C to prevent recurrent anterior corneal pathology. Am J Ophthalmol 142:490, 2006;
Barron BA et al: Herpetic Eye Disease Study. A controlled trial of oral acyclovir for herpes simplex stromal keratitis. Ophthalmology
101:1871, 1994; Dinh R et al: Recurrent of corneal dystrophy after excimer laser phototherapeutic keratectomy.
Ophthalmology 106:1490, 1999; Marcon AS, Rapuano CJ: Excimer laser phototherapeutic keratectomy retreatment of
anterior basement membrane dystrophy and Salzmann’s nodular degeneration with topical mitomycin C. Cornea 21:828, 2002;
Muller LT et al: Transepithelial phototherapeutic keratectomy/photorefractive keratectomy with adjunctive mitomycin-C for
complicated LASIK flaps. J Cataract Refract Surg 31:291, 2005; Rapuano CJ: Excimer laser phototherapeutic keratectomy
in eyes with anterior corneal dystrophies: preoperative and postoperative ultrasound biomicroscopic examination and short-term
clinical outcomes with and without an antihyperopia treatment. Trans Am Ophthalmol Soc 101:371, 2003; Rapuano CJ: Excimer
laser phototherapeutic keratectomy: long-term results and practical considerations. Cornea 16:151, 1997; Sharma N et
al: Indications and outcomes of phototherapeutic keratectomy in the developing world. Cornea 27:44, 2008; Steinert RF et
al: Results of phototherapeutic keratectomy in the management of flap striae after LASIK. Ophthalmology 111:740, 2004; Vinciguerra
P et al: Long-term follow-up of ultrathin corneas after surface retreatment with phototherapeutic keratectomy. J Cataract
Refract Surg 31:82, 2005. Weisenthal RW et al: Photorefractive keratectomy for treatment of flap complications in
laser in situ keratomileusis. Cornea 22:399, 2003; Wilhelmus KR et al: Herpetic Eye Disease Study. A controlled trial of
topical steroids for herpes simplex stromal keratitis. Ophthalmology 101:1883, 1994.
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