From Massachusetts Eye and Ear Infirmary (SPP, MMS, RP), Boston, Massachusetts; and Serdang Hospital (MMS), Ministry of Health, Selangor, Malaysia.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Roberto Pineda, MD, Massachusetts Eye and Ear Infirmary, Cornea and Refractive Surgery Service, 243 Charles Street, Boston, MA 02114.
Posterior polymorphous dystrophy is an endothelial dystrophy typically presenting after the third or fourth decades of life that is characterized by vesicular lesions, band lesions, or diffuse opacities at the level of Descemet’s membrane and endothelium. Broad peripheral anterior synechiae are found in 27% of patients and elevated intraocular pressure in 14% of patients.1 Keratoconus and keratoglobus have been described as stromal dystrophies, with keratoglobus at one extreme of the spectrum. Keratoconus is a progressive bilateral non-inflammatory corneal ectasia characterized by thinning of the corneal stroma and progressive conical corneal protrusion resulting in reduced vision and keratoglobus by limbus-to-limbus corneal thinning, particularly mid-peripherally (one-third to one-fifth of normal corneal thickness), with keratometry readings as high as 60 diopters.2 The diagnosis of keratoconus is frequently made in adolescence through young adulthood. Keratoglobus, typically congenital, may also present as an acquired form in patients with diseases such as hyperthyroidism and vernal keratoconjunctivitis.3
There are several case reports of posterior polymorphous dystrophy occurring in conjunction with keratoconus, even though they affect structurally different layers of the cornea, and these often present at a young age, especially in familial cases.4–6 There is one case report of posterior polymorphous dystrophy in association with keratoglobus in a 34-year-old woman.7 We report a case of a 13-year-old boy with both posterior polymorphous dystrophy and keratoglobus documented by anterior segment imaging and confocal microscopy.
A 13-year-old boy presented to the cornea division complaining of gradually progressive deterioration of vision in both eyes. He also complained of bilateral photophobia and regular headaches. Five years prior to presentation, at age 8 years, he had been diagnosed as having posterior polymorphous dystrophy. General medical history was significant for seasonal allergies and asthma. There was no maternal family history of eye disease and paternal history was unknown.
On examination, best spectacle-corrected visual acuity was 20/30 in the right eye and 20/40 in the left eye with a refraction of −3.75 −4.25 × 008 and −4.50 −1.75 × 180, respectively. Slit-lamp examination revealed scattered corneal endothelial scars with scalloped borders in both eyes that were greater in the left eye than the right eye. No corneal thinning, epithelial edema, stromal haze, or guttae were noted in either eye. The anterior chambers were deep and quiet. No iridocorneal adhesions or iris transillumination defects were appreciated.
Confocal microscopy (Heidelberg Retina Tomograph, Cornea Module; Heidelberg Engineering, Heidelberg, Germany) showed an endothelial monolayer disrupted by areas of diminished discrete areas of loss of endothelial cells with the classic hyporeflective bands consistent with posterior polymorphous dystrophy (Fig. 1).8
Figure 1. Confocal Imaging of Endothelium of the Right Eye. Normal-Appearing Endothelium (superior Half of Image) Is Adjacent to Disrupted Endothelium Displaying Hyporeflective Banding (inferior Half of Image).
Imaging of the eye with the Pentacam camera (PentacamHR; Oculus Optikgreräte GmbH, Wetzlar, Germany) showed diffusely steep corneas with keratometry readings of 55.1 D at 10.6° and 59.2 D at 100.6° in the right eye and 55.4 D at 179.7° and 57.7 D at 89.7° in the left eye (Fig. 2A). This was confirmed on auto-keratometry. Posterior elevation map with best fit sphere in both eyes revealed central steepening (Fig. 2B). Corneal thickness maps showed thicker corneas in both eyes with central corneal thickness of 615 and 596 μm in the right and left eyes, respectively (Fig. 2C).
Figure 2. Pentacam (Pentacamhr; Oculus Optikgreräte GmbH, Wetzlar, Germany) Data of the Corneas of Both Eyes. (A) Sagittal Curvature Map Showing Diffusely Steep Corneas. (B) Posterior Elevation Map to Best Fit Sphere Showing Central Elevation. (C) Corneal Thickness Map Demonstrating Thick Corneas.
Based on clinical examination and ancillary testing, these findings were consistent with a combined diagnosis of posterior polymorphous dystrophy and keratoglobus.
Posterior polymorphous dystrophy in association with keratoconus has been previously described in several case reports. These reports reveal the classic clinical and topographical findings of keratoconus in association with posterior polymorphous dystrophy.4,6 Many of these cases have been described in children and young adults, often with a positive family history of posterior polymorphous dystrophy or keratoconus, with either one as the presenting diagnosis or with concurrent diagnoses. This case is the second report of posterior polymorphous dystrophy in association with keratoglobus.7 Both cases displayed typical findings of posterior polymorphous dystrophy in association with diffuse steepening of the cornea characteristic of keratoglobus but without associated thinning. Neither this nor the previously reported case has shown the typical features of keratoconus such as Fleischer rings, apical thinning, or Vogt’s striae, suggesting that these two cases may represent different pathophysiologic mechanisms compared to the more frequently noted association with keratoconus.
Keratoglobus in children is typically thought of as a congenital disorder, often associated with Leber’s congenital amaurosis or blue sclera syndrome. In adults, it has also been suggested as an acquired ectatic disorder seen in thyroid ophthalmopathy and vernal keratoconjunctivits.2,3 Based on our case and that of Harissi-Dagher et al.,7 it is unclear whether keratoglobus with posterior polymorphous dystrophy has an acquired or congenital etiology.
Mutations in the VSX1 homeobox gene on chromosome 20q11 were initially noted in patients with familial posterior polymorphous dystrophy or keratoconus.9–11 The presence of mutations in a single gene implicated in both diseases makes it tempting to speculate that both are related to a similar pathophysiologic mechanism and that keratoglobus may represent an extreme of the spectrum in keratoconus. However, more recent studies have not found mutations in the VSX1 genomic sequence in families with posterior polymorphous dystrophy, but VSX1 mutations continue to be found, even in unrelated patients with keratoconus.12
The current case suggests that ophthalmologists caring for children with either posterior polymorphous dystrophy or keratoglobus should be aware that the two diseases may occur concurrently. Careful examination should be conducted to evaluate for both to optimize visual outcome in these children.
- Starck T, Hersh PS, Kenyon KR. Corneal dysgenesis, dystrophies, and degenerations. In: Albert DM, Jakobiec FA, Azar DT, Gragoudas ES, eds. Principles and Practice of Ophthalmology, 2nd ed. Philadelphia: W. B. Saunders Company; 2000:695–755.
- Cameron JA. Keratoglobus. Cornea. 1993;12:124–130. doi:10.1097/00003226-199303000-00006 [CrossRef]
- Krachmer JH, Feder RS, Belin MW. Keratoconus and related non-inflammatory corneal thinning disorders. Surv Ophthalmol. 1984;28:293–322. doi:10.1016/0039-6257(84)90094-8 [CrossRef]
- Bechara SJ, Grossniklaus HE, Waring GO 3rd, Wells JA 3rd, . Keratoconus associated with posterior polymorphous dystrophy. Am J Ophthalmol. 1991;112:729–731.
- Driver PJ, Reed JW, Davis RM. Familial cases of keratoconus associated with posterior polymorphous dystrophy. Am J Ophthalmol. 1994;118:256–257.
- Blair SD, Seabrooks D, Shields WJ, Pillai S, Cavanagh HD. Bilateral progressive essential iris atrophy and keratoconus with coincident features of posterior polymorphous dystrophy: a case report and proposed pathogenesis. Cornea. 1992;11:255–261.
- Harissi-Dagher M, Dana RM, Jurkunas U. Keratoglobus in association with posterior polymorphous dystrophy. Cornea. 2007;26:1288–1291. doi:10.1097/ICO.0b013e3181557692 [CrossRef]
- Chiou AG, Kaufman SC, Beuerman RW, Maitchouk D, Kaufman HE. Confocal microscopy in posterior polymorphous corneal dystrophy. Ophthalmologica. 1999;213:211–213. doi:10.1159/000027423 [CrossRef]
- Heon E, Greenberg A, Kopp KK, et al. VSX1: a gene for posterior polymorphous dystrophy and keratoconus. Hum Mol Genet. 2002;11:1029–1036. doi:10.1093/hmg/11.9.1029 [CrossRef]
- Aldave AJ, Yellore VS, Salem AK, et al. No VSX1 gene mutations associated with keratoconus. Invest Ophthalmol Vis Sci. 2006;47:2820–2822. doi:10.1167/iovs.05-1530 [CrossRef]
- Mok J-W, Baek S-J, Joo C-K. VSX1 gene variants are associated with keratoconus in unrelated Korean patients. J Hum Genet. 2008;53:842–849. doi:10.1007/s10038-008-0319-6 [CrossRef]
- Hosseini MS, Herd S, Vincent AL, Heon E. Genetic analysis of chromosome 20-related posterior polymorphous corneal dystrophy: genetic heterogeneity and exclusion of three candidate genes. Molecular Vision. 2008;14:71–80.