Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Congenital Clouding of the Cornea Workup

  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Hampton Roy, Sr, MD  more...
 
Updated: Jan 21, 2016
 

Laboratory Studies

Corneal clouding is a clinical and not a laboratory finding unless it is due to mucopolysaccharidoses.

If MPS VI is suspected, quantification of glycosaminoglycans (GAGs) in the urine and measurement of N -acetylgalactosamine-4-sulfatase (ARSB) activity in leukocytes may be warranted.

In addition to the mucopolysaccharidoses, the differential diagnosis of bilateral corneal stromal opacification includes HDL-deficiency diseases (eg, LCAT deficiency, Tangier disease, fish-eye disease), Schnyder crystalline stromal dystrophy, cystinosis, gout, and mucolipidoses. Scheie syndrome (MPS I S) may easily be detected by finding alpha-L-iduronidase deficiency in leukocytes and increased mucopolysaccharide levels in the urine.

Next

Imaging Studies

The imaging studies below may be performed depending on the physical findings to assess for conditions that may accompany corneal clouding.

Newborn PCG can be recognized at birth because of the associated corneal opacification. The evaluation of congenital glaucoma should include the following: a complete eye examination, including anterior segment evaluation, with slit lamp biomicroscopy (see image below), funduscopy, tonometry, and gonioscopy.

Congenital stromal dystrophy. The cornea is partic Congenital stromal dystrophy. The cornea is particularly opaque in the anterior stroma by slit-lamp biomicroscopy. Courtesy of Wikipedia (© 2009 Klintworth; licensee BioMed Central Ltd).

Ocular examination of a patient with congenital glaucoma can reveal anterior segment abnormalities of the cornea, iris, and filtration angle as well as related elevated IOP. A-scan ultrasonography can reveal an enlarged globe (buphthalmos). Genetic analysis can be done to detect syndromes associated with congenital glaucoma.

Indirect gonioscopy can be performed with a Goldmann lens. IOP can be measured with a Goldmann applanation tonometer. Photographs can be taken of the anterior segment and all 4 quadrants of the iridocorneal angle to record the presence of abnormalities. The iridocorneal angle can be graded according to the classification proposed by Spaeth.

Photoscreening is designed to detect abnormalities in children's eyes, particularly abnormal refractive errors, which can lead to amblyopia. Photoscreening can also detect congenital glaucoma.

Tonometry is an essential component of the examination but can be the most difficult part of the examination with a fractious child.

Inspection and examination of the anterior segment are facilitated by the use of a penlight and a handheld slit lamp, which allow maneuverability regardless of the child's position.

The optic nerve head may be examined with a direct or indirect ophthalmoscope.

MRI of the abdomen is indicated to rule out genitourinary abnormalities.

MRIs of the brain and spinal cord are also indicated to rule out neurologic defects.

Echocardiography is indicated to rule out cardiac defects.

Ocular ultrasonography may be useful in assessing other ocular abnormalities. This includes patients with type II and VI mucopolysaccharidosis (MPS) in whom clinically marked corneal clouding is present; measuring the corneal thickness can evaluate intraocular pressure and possible coexistent glaucoma.[28]

Ultrasound biomicroscopy (UBM) is often helpful in the evaluation of anterior segment structures that cannot be observed clearly because of the corneal opacity. UBM and histopathology can play a role in the evaluation of sclerocornea.[29]

B-scan ultrasonography is necessary to evaluate the posterior segment if the corneal opacity is dense and central.

CT scanning is indicated to help diagnose protuberant congenital corneal opacities.

Previous
Next

Other Tests

Hearing tests may be performed to rule out hearing abnormalities.

Corneal clouding, as observed by using a slit lamp, may be used in the differential diagnosis of mucopolysaccharidoses. Corneal clouding is present in MPS I, VI, and VII but absent in MPS II.

Previous
Next

Procedures

Maroteaux-Lamy syndrome (MPS VI) can be evaluated by means of slit lamp biomicroscopy, Orbscan II slit scanning elevation topography, and in vivo confocal microscopy.

Slit lamp biomicroscopy can reveal bilateral, altered corneal transparency involving the posterior half of the stroma.

Funduscopy reveals bilateral small, crowded optic discs, and radial macula retinal folds.

On in vivo confocal microscopy, the middle and posterior stroma can be visualized and show well-defined, unusually shaped keratocytes. These cells contain single or several hyporeflective regions with well-defined borders 1-11.6 micrometers in diameter. These abnormal keratocytes are particularly abundant in the posterior stroma and sparse in the anterior stroma.

Previous
Next

Histologic Findings

Histopathologic results are often diagnostic for Peters anomaly. Histologic findings show either thinning or absence of the Descemet membrane or the endothelium. The lens may be normal, or it may be cataractous and adhere to the cornea. The stromal lamellae are irregular and more closely packed. Undifferentiated iris strands attach to the posterior surface of the cornea.

Epithelial corneal nerve morphology and anterior corneal nerve structure in the early stages of congenital aniridic keratopathy have been more fully explicated.[30] Moreover,

the clinical features involved with anterior segment dysgenesis involved with congenital corneal opacities were explicated.[31]

Perry states, "Histopathologic findings include absence of Descemet's membrane, corneal endothelium, and, usually, Bowman's membrane, as well as thinning of corneal stroma. The defects in Descemet's membrane, although usually single and central, may be multiple and isolated to the periphery, or they may be limited to an area of adhesion of iris. Descemet's membrane has been found to have embryonal ultrastructural characteristics combined with attenuated endothelium. The corneal stromal lamellae are more irregular and closely packed when compared to normal stromal lamella."[7]

Histochemical studies have shown absence of keratan sulfate in both the cornea and the sclera.

Immunohistochemical studies have shown increased amounts of fibronectin and type VI collagen in the corneas of patients with Peters anomaly.

In MPS VI B, the histopathologic and ultrastructural features of the corneal button reveal the accumulation of membrane-bound vacuoles containing fibrillogranular and lamellated material in keratocytes and endothelial cells and thinning of the Descemet membrane with excrescences. Other MPS diseases can have other histologic findings.

A 4-month-old male infant with severe corneal opacity since birth had buphthalmos, increased IOP, and corneal opacity with neovascularization.[27] (See Clinical variant of Sanfilippo syndrome in History.) Histopathologic examination of the corneal button showed homogeneous thickening of the Bowman layer and pinkish intracytoplasmic substances in the corneal stroma. The Alcian blue stain was positive, consistent with MPS of the cornea. The manifestation of this case may be a clinical variant of Sanfilippo syndrome (MPS III).

In sclerocornea, the numbers of collagen fibrils are increased and their diameter varies in the normal corneal stroma. The Descemet membrane appears thin. Scleralization of the collagen fibrils often stops in the pre-Descemet membrane region, permitting deep lamellar keratoplasty.

In cornea plana, the corneal tissue is histologically normal. The axial length of eyes that contain cornea plana is normal.

Perry notes that, in corneal keloids, "Stromal nodules are composed of proliferating myofibroblasts, activated fibroblasts, and haphazardly arranged fascicles of collagen. Immunohistochemical stains show spindle cells that express immunoreactivity for vimentin and alpha smooth muscle actin. Keloid formation may be the result of excessive local delivery of amino acids and unknown noxious substances through leaking corneal vessels."[7]

Perry notes that, in corneal dermoids, "Histologically, the corneal epithelium may be keratinized. Bowman's membrane often is absent. The stroma is replaced to a variable degree by irregularly arranged, dense, vascularized, collagenous connective tissue containing hair follicles, hair shafts, sebaceous glands, fat, smooth muscle, striated muscle, cartilage, teeth, or bone. The mass may be either cystic or solid."[7]

Perry notes that, in congenital corneal ectasia, "Histologically, the corneal epithelium has normal thickness but may be keratinized secondary to exposure. Often, local attenuation of Bowman's membrane occurs. The stroma is thickened, disorganized, hypercellular, and vascularized. A double layer of pigment-containing cells lines the posterior corneal stroma. Usually, no sign of an inflammatory infiltrate is present. Descemet's membrane and corneal endothelium are absent."[7]

Perry notes that, in congenital hereditary stromal dystrophy, "The collagen of the corneal stroma by electron microscopy consists of alternating layers of small-diameter collagen fibrils of approximately one-half the normal fibril diameter. Also, the anterior banded portion of Descemet's membrane is poorly developed. The endothelium is normal."[7]

Perry notes that, in congenital hereditary endothelial dystrophy, "Histologically, increased diameter of stromal collagen fibrils may produce a thick cornea. Descemet's membrane is thickened in a manner similar to that found with Fuchs' endothelial dystrophy, implying a corneal endothelial abnormality."[7]

In posterior polymorphous dystrophy, Perry notes that, histologically, "Descemet's membrane may be focally or diffusely thickened. Endothelial cells are multilayered and have desmosomes and intracytoplasmic filaments that are characteristic of epithelial cells. A layer of cells may be present beneath the corneal epithelium, but epithelial edema is not common. Iridocorneal adhesions, glassy membranes, and pupillary ectropion, which are changes found in the iridocorneal endothelial syndrome, also may be present in this condition."[7]

Previous
 
 
Contributor Information and Disclosures
Author

Noah S Scheinfeld, JD, MD, FAAD Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Abbvie<br/>Received income in an amount equal to or greater than $250 from: Optigenex<br/>Received salary from Optigenex for employment.

Coauthor(s)

Benjamin D Freilich, MD, FACS Assistant Clinical Professor, Department of Ophthalmology, Icahn School of Medicine at Mount Sinai; Director of Retina Service, Bronx Veterans Administration Medical Center

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Christopher J Rapuano, MD Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Hospital

Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Ophthalmological Society, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, International Society of Refractive Surgery, Cornea Society, Eye Bank Association of America

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cornea Society, Allergan, Bausch & Lomb, Bio-Tissue, Shire, TearScience, TearLab<br/>Serve(d) as a speaker or a member of a speakers bureau for: Allergan, Bausch & Lomb, Bio-Tissue, TearScience.

Chief Editor

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Additional Contributors

Richard W Allinson, MD Associate Professor, Department of Ophthalmology, Texas A&M University Health Science Center; Senior Staff Ophthalmologist, Scott and White Clinic

Richard W Allinson, MD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

Jonathan Freilich, MD, FACS Clinical Instructor, Department of Ophthalmology, Mount Sinai School of Medicine; Consulting Staff, Department of Ophthalmology, Mount Sinai Hospital, St Luke's Roosevelt Hospital Center

Disclosure: Nothing to disclose.

References
  1. Bhat YR, Sanoj KM. Images in Clinical Practices. Sclerocornea. Indian Pediatrics. 2005 Mar 17. 42:42. [Full Text].

  2. EyeMDLink. Congenital hereditary endothelial dystrophy. Available at http://www.allaboutvision.com/conditions/.

  3. Hand CK, Harmon DL, Kennedy SM, FitzSimon JS, Collum LM, Parfrey NA. Localization of the gene for autosomal recessive congenital hereditary endothelial dystrophy (CHED2) to chromosome 20 by homozygosity mapping. Genomics. 1999 Oct 1. 61(1):1-4. [Medline].

  4. Miller MM, Butrus S, Hidayat A, Wei LL, Pontigo M. Corneoscleral transplantation in congenital corneal staphyloma and Peters' anomaly. Ophthalmic Genet. 2003 Mar. 24(1):59-63. [Medline].

  5. Desir J, Abramowicz M. Congenital hereditary endothelial dystrophy with progressive sensorineural deafness (Harboyan syndrome). Orphanet J Rare Dis. 2008 Oct 15. 3:28. [Medline]. [Full Text].

  6. Waizenegger UR, Kohnen T, Weidle EG, Schütte E. [Congenital familial cornea plana with ptosis, peripheral sclerocornea and conjunctival xerosis]. Klin Monatsbl Augenheilkd. 1995 Aug. 207(2):111-6. [Medline].

  7. Perry HD, Cameron JD. Congenital corneal opacities. Available at http://www.ophthalmic.hyperguides.com.

  8. Bower KS, Edwards JD, Wagner ME, Ward TP, Hidayat A. Novel corneal phenotype in a patient with alport syndrome. Cornea. 2009. 28:599-606. [Medline].

  9. Haider AS, Ganesh A, Al-Kindi A, Al-Hinai A, Al-Kharousi N, Al-Yaroubi S, et al. New Ocular Associations in Sanjad-Sakati Syndrome: Case report from Oman. Sultan Qaboos Univ Med J. 2014 Aug. 14(3):e401-4. [Medline].

  10. Chandravanshi SL. Encephalocraniocutaneous lipomatosis: a case report and review of the literature. Indian J Ophthalmol. 2014 May. 62(5):622-7. [Medline].

  11. Resende GM, Lupinacci AP, Árieta CE, Costa VP. Central corneal thickness and intraocular pressure in children undergoing congenital cataract surgery: a prospective, longitudinal study. Br J Ophthalmol. 2012 Sep. 96(9):1190-4. [Medline].

  12. Gatzioufas Z, Labiris G, Stachs O, et al. Biomechanical profile of the cornea in primary congenital glaucoma. Acta Ophthalmol. 2013 Feb. 91(1):e29-34. [Medline].

  13. Murphy MJ, Polok BK, Schorderet DF, Cleary ML. Essential role for Pbx1 in corneal morphogenesis. Invest Ophthalmol Vis Sci. 2010 Feb. 51(2):795-803. [Medline]. [Full Text].

  14. Mellgren AE, Bruland O, Vedeler A, Saraste J, Schönheit J, Bredrup C, et al. Development of congenital stromal corneal dystrophy is dependent on export and extracellular deposition of truncated decorin. Invest Ophthalmol Vis Sci. 2015 May;. 56(5):2909-15. [Medline].

  15. Wang KJ, Wang BB, Zhang F, Zhao Y, Ma X, Zhu SQ. Novel beta-crystallin gene mutations in Chinese families with nuclear cataracts. Arch Ophthalmol. Mar 2011. 3:337-43. [Medline].

  16. Kao WW, Liu CY. Roles of lumican and keratocan on corneal transparency. Glycoconj J. 2002 May-Jun. 19(4-5):275-85. [Medline].

  17. Roos L, Bertelsen B, Harris P, Bygum A, Jensen H, Grønskov K, et al. Case report: a novel KERA mutation associated with cornea plana and its predicted effect on protein function. BMC Med Genet. 2015 Jun 23. 16:40. [Medline].

  18. Rezende RA, Uchoa UB, Uchoa R, Rapuano CJ, Laibson PR, Cohen EJ. Congenital corneal opacities in a cornea referral practice. Cornea. 2004 Aug. 23(6):565-70. [Medline].

  19. Bermejo E, Martínez-Frías ML. Congenital eye malformations: clinical-epidemiological analysis of 1,124,654 consecutive births in Spain. Am J Med Genet. 1998 Feb 17. 75(5):497-504. [Medline].

  20. el-Gilany AH, el-Fedawy S, Tharwat M. Causes of blindness and needs of the blind in Mansoura, Egypt. East Mediterr Health J. 2002 Jan. 8(1):6-17. [Medline].

  21. Floyd MS, Kwon YH, Shah S, Benson C, Longmuir SQ. Unilateral congenital glaucoma in a child with optic nerve aplasia. J AAPOS. Apr 2011. 2:200-2. [Medline].

  22. Hwang JM, Chung DC, Traboulsi EI. A new syndrome of hereditary congenital corneal opacities, cornea guttata, and corectopia. Arch Ophthalmol. 2003 Jul. 121(7):1053-4. [Medline].

  23. Cibis GW. Congenital glaucoma. J Am Optom Assoc. 1987 Sep. 58(9):728-33. [Medline].

  24. Edward DP, Li J, Sawaguchi S, Sugar J, Yue BY, Tso MO. Diffuse corneal clouding in siblings with fetal alcohol syndrome. Am J Ophthalmol. 1993 Apr 15. 115(4):484-93. [Medline].

  25. Aldave AJ, Eagle RC Jr, Streeten BW, Qi J, Raber IM. Congenital corneal opacification in De Barsy syndrome. Arch Ophthalmol. 2001 Feb. 119(2):285-8. [Medline].

  26. O'Neill JF. The ocular manifestations of congenital infection: a study of the early effect and long-term outcome of maternally transmitted rubella and toxoplasmosis. Trans Am Ophthalmol Soc. 1998. 96:813-79. [Medline].

  27. Lin SC, Hu FR, Hou JW, Yao YT, Wang TR, Hung PT. Corneal opacity and congenital glaucoma associated with massive heparan sulfaturia: report of one case. Acta Paediatr Taiwan. 1999 Jan-Feb. 40(1):46-9. [Medline].

  28. Kottler U, Demir D, Schmidtmann I, Beck M, Pitz S. Central corneal thickness in mucopolysaccharidosis II and VI. Cornea. 2010 Mar. 29(3):260-2. [Medline].

  29. Kim T, Cohen EJ, Schnall BM, Affel EL, Eagle RC Jr. Ultrasound biomicroscopy and histopathology of sclerocornea. Cornea. 1998 Jul. 17(4):443-5. [Medline].

  30. Eden U, Fagerholm P, Danyali R, Lagali N. Pathologic Epithelial and Anterior Corneal Nerve Morphology in Early-Stage Congenital Aniridic Keratopathy. Ophthalmology. April 2012. [Medline].

  31. Shigeyasu C, Yamada M, Mizuno Y, Yokoi T, Nishina S, Azuma N. Clinical features of anterior segment dysgenesis associated with congenital corneal opacities. Cornea. March 2012. 31:293-8. [Medline].

  32. Coulson-Thomas VJ, Caterson B, Kao WW. Transplantation of human umbilical mesenchymal stem cells cures the corneal defects of mucopolysaccharidosis VII mice. Stem Cells. 2013 Oct. 31(10):2116-26. [Medline]. [Full Text].

  33. Reidy JJ. Penetrating keratoplasty in infancy and early childhood. Curr Opin Ophthalmol. 2001 Aug. 12(4):258-61. [Medline].

  34. Michaeli A, Markovich A, Rootman DS. Corneal transplants for the treatment of congenital corneal opacities. J Pediatr Ophthalmol Strabismus. 2005 Jan-Feb. 42(1):34-44. [Medline].

  35. Al-Torbak AA. Outcome of combined Ahmed glaucoma valve implant and penetrating keratoplasty in refractory congenital glaucoma with corneal opacity. Cornea. 2004 Aug. 23(6):554-9. [Medline].

  36. Miller MM, Butrus S, Hidayat A, Wei LL, Pontigo M. Corneoscleral transplantation in congenital corneal staphyloma and Peters' anomaly. Ophthalmic Genet. 2003 Mar. 24(1):59-63. [Medline].

  37. Mandal AK, Gothwal VK, Bagga H, Nutheti R, Mansoori T. Outcome of surgery on infants younger than 1 month with congenital glaucoma. Ophthalmology. 2003 Oct. 110(10):1909-15. [Medline].

  38. Frueh BE, Brown SI. Transplantation of congenitally opaque corneas. Br J Ophthalmol. 1997 Dec. 81(12):1064-9. [Medline].

  39. Bredrup C, Knappskog PM, Majewski J, Rodahl E, Boman H. Congenital stromal dystrophy of the cornea caused by a mutation in the decorin gene. Invest Ophthalmol Vis Sci. 2005 Feb. 46(2):420-6. [Medline].

  40. Cassidy L. Paediatric cataract. March 9 2001. optometrytoday. Available at http://www.optometry.co.uk/files/e8cf2c379b358b7d42e25bdfa54a9abf_cassidy20010309.pdf. Accessed: March 12, 2011.

  41. Ciralsky J, Colby K. Congenital corneal opacities: a review with a focus on genetics. Semin Ophthalmol. 2007 Oct-Dec. 22:241-6. [Medline].

  42. Hansen L, Eiberg H, Rosenberg T. Novel MAF mutation in a family with congenital cataract-microcornea syndrome. Mol Vis. 2007 Oct 18. 13:2019-22. [Medline].

  43. Hansen L, Yao W, Eiberg H, Kjaer KW, Baggesen K, Hejtmancik JF, et al. Genetic heterogeneity in microcornea-cataract: five novel mutations in CRYAA, CRYGD, and GJA8. Invest Ophthalmol Vis Sci. 2007 Sep. 48(9):3937-44. [Medline].

  44. Lisch W. Corneal dystrophy (CD)-induced pain and visual impairment in childhood. Klin Monbl Augenheilkd. 2013 Jun. 230:582-6.

  45. Parthasarathy A, Naumann GO. Coexistent congenital hereditary endothelial dystrophy and congenital glaucoma. Cornea. 2009 Apr. 28(3):365; author reply 365-6. [Medline].

  46. Sherman MD. Dermoids, Limbal. Medscape Reference. 2010. [Full Text].

  47. Stone DU, Siatkowski RM. Congenital retinal dystrophy and corneal opacity in trisomy 8 mosaicism. J AAPOS. 2005 Jun. 9(3):290-1. [Medline].

  48. Tewfik TL. Manifestations of Craniofacial Syndromes. Medscape Reference Journal [serial online]. 2010. [Full Text].

  49. Thiagalingam S, Jakobiec FA, Chen T, Michaud N, Colby KA, Walton DS. Corneal anomalies in newborn primary congenital glaucoma. J Pediatr Ophthalmol Strabismus. 2009 Jul-Aug. 46(4):241-4. [Medline].

  50. Wimplinger I, Shaw GM, Kutsche K. HCCS loss-of-function missense mutation in a female with bilateral microphthalmia and sclerocornea: a novel gene for severe ocular malformations?. Mol Vis. 2007 Aug 27. 13:1475-82. [Medline].

 
Previous
Next
 
Congenital stromal dystrophy. The cornea is particularly opaque in the anterior stroma by slit-lamp biomicroscopy. Courtesy of Wikipedia (© 2009 Klintworth; licensee BioMed Central Ltd).
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.