Stromal keratitis and corneal conditions involving edema are traditionally followed with biomicroscopy, occasionally with adjunct anterior segment photography, or ultrasound pachymetry. Spectral-domain optical coherence tomography (SD-OCT) is a relatively new technology that also may be useful for monitoring such conditions.
Biomicroscopy enables direct observation of the cornea. It allows the clinician to subjectively observe the entire cornea from several angles and make clinical comparisons across time. Spectral-domain optical coherence tomography has no database to elucidate the nature of opacities and abnormalities but provides valuable adjunctive information to biomicroscopy of what is transpiring within the thickness of the cornea and helps identify the corneal layers involved. Photography may be used in conjunction with biomicroscopy to document improvement or progression in many conditions. Ultrasound pachymetry has been used to follow the corneal thickness in keratitis.1,2 Decreases in pachymetry readings correlate to a likely reduction in edema. However, this may be imprecise because the pachymeter probe is handheld in space and repeat measurements designed to gauge clinical progress depend on the examiner repeating measurements in exactly the same place on the cornea as well as positioning the probe exactly perpendicular to the corneal surface for the most precise measurement. Spectral-domain OCT is an adjunct that can be used in conjunction with, or in replacement of, ultrasound pachymetry to monitor corneal conditions through follow-up.
Anterior segment SD-OCT is a recent development that may also be used to follow corneal edema. This technology allows not only direct objective comparison of corneal thickness but a two-dimensional image showing the location and extent of edema throughout the cornea. As illustrated in the following case reports, SD-OCT can be a useful adjunctive tool for following patients being managed therapeutically for stromal edema.
A 34-year-old Hispanic man presented for consultation, complaining of cloudiness over the vision in his left eye for 3 weeks. The patient denied any pain or discomfort. He reported a positive health history for diabetes with recently uncontrolled blood glucose levels. He reported taking metformin for his diabetes. He denied any history of previous ocular health issues.
The patient’s uncorrected presenting visual acuity was 20/20 in the right eye and 20/100 in the left, improving to 20/50 with pinhole. Pupils, confrontation field, and version testing were normal.
Biomicroscopic evaluation showed mild posterior blepharitis in each eye. Examination of the palpebral conjunctivae revealed only trace papillae in both eyes, with the absence of any follicular response. The cornea in the right eye was clear, and the anterior chamber was deep and quiet. Examination of the left cornea showed a disc-shaped area of stromal edema, microcystic edema, large limbal infiltrates, endothelial folds, and keratic precipitates (Fig. 1). Staining with sodium fluorescein showed punctate staining and some negative staining associated with areas of microcystic edema. Corneal sensitivity testing was performed with a cotton wisp, showing greater sensitivity in the left eye than the right eye. The view into the anterior chamber was mildly compromised secondary to the corneal edema.
Intraocular pressure by Goldmann tonometry pressures was 14 mm Hg in the right eye and 16 mm Hg in the left eye. Dilated fundus examination revealed normal maculae, optic nerves, vessels, and retinae in both eyes, although a slightly hazy view was obtained OS. There was no evidence of posterior uveitis.
The patient was diagnosed as having disciform keratitis of unknown, although presumed viral, origin. The patient was given a drop of 0.25% scopolamine in the left eye in the office and prescribed prednisolone acetate 1% to use every hour and moxifloxacin 0.5% to use prophylactically every 2 hours in the left eye. In that corneal sensitivity testing was negative and he had no history of dendritic keratitis, the condition was not definitively thought to be herpetic and antiviral medications were not used at this time.
He was seen the next day and reported improvement in his vision. The uncorrected visual acuity in his left eye improved to 20/80, with pinhole improvement of 20/60. A decrease in edema was subjectively noted biomicroscopically. Another drop of 0.25% scopolamine was instilled in the left eye, and the patient was advised to continue his medications and return for a follow-up visit in 2 days.
During his third visit, 3 days after his initial visit, he reported further improvement in his vision. His visual acuity was measured at 20/70 in the left eye, with improvement to 20/40 with pinhole. Intraocular pressures were measured by applanation at 12 mm Hg in the right eye and 18 mm Hg in the left eye. Slight improvement in edema was noted biomicroscopically. At this visit, SD-OCT images (Cirrus 4000; Carl Zeiss Meditec, Dublin, CA) using the Anterior Segment Cube program were taken in both eyes (Figs. 2, 3) and the maximum thickness was compared and found to be 540 μm in the right eye and 900 μm in the left eye. Keratic precipitates were visualized on the endothelium of the left eye. This program evaluation is based on a 4 by 4–mm data cube captured by the Anterior Segment Cube 512 by 128 scan, which provides qualitative and quantitative evaluation of the cornea, including visualization of pathology and measurement of corneal thickness. A slice navigator allows for a simultaneous view of a selected portion of the cornea with OCT image display.
During the next month, medications were tapered as dictated by clinical improvement and decreasing corneal thickness and edema. Intraocular pressures were normal at all subsequent visions. Reduction of corneal thickness commensurate with biomicroscopically appreciated resolution of edema, as well as a reduction in the size of keratic precipitates, was quantified and documented with SD-OCT images (Fig. 4).
A 43-year-old white man reported for consultation 7 days after having been diagnosed previously as having dendritic keratitis in the right eye. He had been prescribed trifluridine (Viroptic; Monarch Pharmaceuticals, Greenville, NC), with which he reported poor compliance, and now complained of increased light sensitivity. Pupils, confrontation fields, and version testing were normal. His uncorrected visual acuity was 20/50 in the right eye and improved to 20/40 with pinhole. Vision in the left eye was 20/15 uncorrected. Biomicroscopy of the right eye revealed keratic precipitates, disc-shaped focal stromal edema, and mild punctate epithelial keratitis, with no current evidence of formed dendritic lesions. The patient was diagnosed as having disciform keratitis likely caused by herpes simplex. Evaluation of the anterior chamber revealed a 1+ cellular reaction. All anterior segment findings were normal in the left eye. Goldmann intraocular pressure was measured at 12 mm Hg in both eyes at the first visit and never rose about 15 mm Hg in either eye during treatment. The patient was restarted on trifluridine 1% every 2 hours in the right eye.
The patient returned in 2 days and reported compliance with the treatment regimen and improvement in his condition. Preliminary testing remained unremarkable. Vision in his right eye improved to 20/40-2, with no improvement with pin hole and remained 20/15 in the left eye. Biomicroscopy of the right eye still showed stromal edema, central keratic precipitates, and mild punctate keratopathy. No dendritic lesion remained. Rare cells and mild flare were noted in the anterior chamber. The left eye remained normal. The patient was diagnosed with resolving viral disciform keratitis OD. Trifluridine 1% was tapered to four times per day and prednisolone acetate 1% was added four times per day in the right eye. Anterior segment SD-OCT imaging of the right eye (Fig. 5) was performed at this visit, demonstrating corneal edema as well as keratic precipitates. The thickness of each image was measured, and the thickest portion measured 708 μm. The patient was followed over appropriate intervals and medications were tapered as clinical findings dictated. Subjective clinical biomicroscopic improvement was correlated with corneal thickness findings via SD-OCT (Fig. 6).
Anterior segment imaging with SD-OCT is a relatively new application of technology previously used solely to image the posterior segment. Spectral-domain OCT imaging occurs by splitting a light beam using interferometry. The light reflects from ocular tissues and is recomposed into a series of A-scans forming an image.3 Anterior segment imaging via the OCT was first described in 1994 by Izatt et al.4 Since then, many reports have used anterior segment OCT for a variety of corneal applications including pre– and post–corneal surgical observations and corneal thickness measurements. Ramos et al.3 stated that the OCT accurately quantifies the thickness of a diseased cornea.
Several reports describe the use of the anterior segment OCT in preoperative and postoperative corneal surgery. One use involved evaluation of changes in corneal thickness and curvature that occur after laser photorefractive keratectomy.5 Wirbelauer et al.6 evaluated recurrent corneal erosion before and after phototherapeutic keratectomy using OCT and were able to obtain noncontact detailed imaging of the epithelial layer as well as corneal thickness measurements. A case report by Ma and associates7 used SD-OCT imaging to locate the exact area of cornea scarring and follow improvement after treatment with phototherapeutic keratectomy.
Anterior segment SD-OCT has also been used to measure corneal thickness. Many studies have shown OCT to be precise in measuring central corneal thickness.8–12 Although a variety of mean differences between ultrasound pachymetry and OCT pachymetry have been found (Table 1), many studies have found a good correlation between ultrasound and OCT pachymetry in the measurement of central corneal thickness.8–10,13 A study by Bechmann et al.8 found that OCT pachymetry on a normal cornea measured lower than ultrasound pachymetry and that the difference was greater when comparing ultrasound with OCT on edematous corneas. Despite the increase in difference, a good correlation remained between the readings of the two instruments.
Clinical observation with biomicroscopy is typically used to follow resolution of keratitis with corneal edema and was the sole method used in the stromal keratitis branch of the Herpetic Eye Disease Study.14 Although biomicroscopy allows direct viewing of the whole cornea, comparisons across time are very subjective and can prove to be difficult in large clinical settings where multiple doctors may follow a single patient. Anterior segment photography may also be used but can show varying clinical pictures depending on the angle and light used. Spectral-domain OCT anterior segment imaging measurements are objective and reduce interobserver variability. Mohamed et al.15 reported that the fast acquisition time coupled with high resolution and the ability to obtain a cross section of the cornea via measurement of back scattered light increased the reliability and repeatability of the OCT. Imaging provided by SD-OCT allows observation that is more detailed than may be obtained by biomicroscopic observation alone. As illustrated in Fig. 7, the precise areas of edema and keratic precipitates may be located. We would recommend that, in cases such as these presented here, maximal value of imaging would dictate SD-OCT measurements be performed at the initial examination and through every follow-up to resolution.
Anterior segment OCT also provides some advantages over ultrasound pachymetry. Ultrasound pachymetry limits readings to one dimension. Optical coherence tomography provides a two-dimensional image that allows variations to be seen in a cross section of the cornea. Another consideration is that ultrasound pachymetry requires an anesthetic, which can be irritating to the cornea, whereas SD-OCT is a noncontact form of imaging that does not require any form of anesthetic. This may be useful in cases in which the cornea is inflamed and further irritation is undesirable. In addition, ultrasound pachymetry was shown to fail in one case of corneal edema noted in acute hydrops. This inability to obtain a reading was attributed to the massive amount of edema observed.8
Decreasing corneal thickness can be used as an indicator of therapeutic success and disease resolution. In most cases of acute keratopathy, there will not be a baseline corneal thickness measurement with which to compare to confirm resolution. In these cases, comparing final corneal thickness between the involved and uninvolved eye will give insight into suspected resolution when near symmetry is achieved.
A limitation is that most current SD-OCTs image only a finite section of the cornea and do not go limbus to limbus. However, in well-circumscribed keratopathies such as disciform keratitis, the involved area can usually be readily identified for imaging. In cases of widespread or diffuse corneal edema, SD-OCT programs that give global pachymetry readings would be most useful.
Current SD-OCTs have an advantage in that corneal involvement can be imaged and measured both horizontally and vertically, potentially giving the operator the ability to measure several thicknesses throughout the lesions. In the absence of registration for anterior segment imaging, multiple horizontal and vertical images will reduce the likelihood that the wrong areas are being compared.
Anterior segment SD-OCT allows objective measurements of corneal thickness and presents an adjunctive method for following various forms of keratitis involving corneal edema with greater accuracy and objectivity than may be appreciated with subjective biomicroscopic evaluation alone. Because OCT is a noncontact instrument, measurements may be taken without the disturbing effects of an anesthetic. This type of imaging is objective and may be useful in clinical settings where there are multiple doctors or in studies where an objective reading is desirable. Spectral-domain OCT should be considered a valuable objective adjunctive test to biomicroscopic evaluation of therapeutic interventions in cases such as disciform keratitis. In the cases presented here, a rapid decrease in corneal thickness is initially noted, supporting presumably a response to therapy and demonstrating the value of SD-OCT early in the disease process. Normal symmetrical corneal thickness was noted after 25 and 33 days, respectively, illustrating a significant role of SD-OCT in the later stages of the disease process, aiding in the decision to discontinue therapy.
There seems to be no disadvantages to using SD-OCT to monitor keratitis resolution as long as it is used in conjunction with visual acuity measurement and biomicroscopy. This article attempts to illustrate a potential adjunctive use of SD-OCT to monitor disease treatment and resolution in conditions that affect corneal thickness.
The authors have no direct financial interest in any products mentioned.
Received September 13, 2013; accepted December 23, 2013.
1. Wilhelmus KR, Sugar J, Hyndiuk RA, Stulting RD. Corneal thickness changes during herpes simplex virus disciform keratitis
. Cornea 2004; 23: 154–7.
2. Loh RS, Chan CM, Ti SE, Lim L, Chan KS, Tan DT. Emerging prevalence of microsporidial keratitis in Singapore: epidemiology, clinical features, and management. Ophthalmology 2009; 116: 2348–53.
3. Ramos JL, Li Y, Huang D. Clinical and research applications of anterior segment optical coherence tomography—a review. Clin Experiment Ophthalmol 2009; 37: 81–9.
4. Izatt JA, Hee MR, Swanson EA, Lin CP, Huang D, Schuman JS, Puliafito CA, Fujimoto JG. Micrometer-scale resolution imaging of the anterior eye in vivo
with optical coherence tomography. Arch Ophthalmol 1994; 112: 1584–9.
5. Wirbelauer C, Scholz C, Hoerauf H, Engelhardt R, Birngruber R, Laqua H. Corneal optical coherence tomography before and immediately after excimer laser photorefractive keratectomy. Am J Ophthalmol 2000; 130: 693–9.
6. Wirbelauer C, Scholz C, Haberle H, Laqua H, Pham DT. Corneal optical coherence tomography before and after phototherapeutic keratectomy for recurrent epithelial erosions. J Cataract Refract Surg 2002; 28: 1629–35.
7. Ma JJ, Tseng SS, Yarascavitch BA. Anterior segment optical coherence tomography for transepithelial phototherapeutic keratectomy in central corneal stromal scarring. Cornea 2009; 28: 927–9.
8. Bechmann M, Thiel MJ, Neubauer AS, Ullrich S, Ludwig K, Kenyon KR, Ulbig MW. Central corneal thickness measurement with a retinal optical coherence tomography device versus standard ultrasonic pachymetry. Cornea 2001; 20: 50–4.
9. Kim HY, Budenz DL, Lee PS, Feuer WJ, Barton K. Comparison of central corneal thickness using anterior segment optical coherence tomography vs. ultrasound pachymetry. Am J Ophthalmol 2008; 145: 228–32.
10. Leung DY, Lam DK, Yeung BY, Lam DS. Comparison between central corneal thickness measurements by ultrasound pachymetry and optical coherence tomography. Clin Experiment Ophthalmol 2006; 34: 751–4.
11. Fishman GR, Pons ME, Seedor JA, Liebmann JM, Ritch R. Assessment of central corneal thickness using optical coherence tomography. J Cataract Refract Surg 2005; 31: 707–11.
12. Li H, Leung CK, Wong L, Cheung CY, Pang CP, Weinreb RN, Lam DS. Comparative study of central corneal thickness measurement with slit-lamp optical coherence tomography and visante optical coherence tomography. Ophthalmology 2008; 115: 796–801 e2.
13. Li Y, Shekhar R, Huang D. Corneal pachymetry mapping with high-speed optical coherence tomography. Ophthalmology 2006; 113: 792–9 e2.
14. Wilhelmus KR, Gee L, Hauck WW, Kurinij N, Dawson CR, Jones DB, Barron BA, Kaufman HE, Sugar J, Hyndiuk RA, Laibson PR, Stulting RD, Asbell PA Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis
. Ophthalmology 1994; 101: 1883–95.
15. Mohamed S, Lee GK, Rao SK, Wong AL, Cheng AC, Li EY, Chi SC, Lam DS. Repeatability and reproducibility of pachymetric mapping with Visante anterior segment-optical coherence tomography. Invest Ophthalmol Vis Sci 2007; 48: 5499–504.