a 22-year - old man presented with severe photophobia and decreased visual acuity in the right eye . he was diagnosed initially with nephropathic and ocular cystinosis at the age of 4 years . the visual acuity was hand motion in the right eye and 4/4 in the left eye . the intraocular pressure was 17 mmhg in the right eye , while that of the left eye could not be measured because the patient was uncooperative . in slit lamp examination , we found the moderate corneal edema and multiple crystal deposits in the right eye and an anterior segment photograph also showed opacity , moderate edema , and multiple progressive refractile polychromatic crystal deposits in the right cornea . cystagon ( cysteamine bitartrate , mylan , france ) eye drops were prescribed , but there was no improvement in the patient 's visual acuity or symptoms . preoperative anterior segment oct ( visante , carl zeiss meditec ) showed hyperreflectivity at the stroma of the cornea , indicating the presence of corneal cystine crystals [ fig . 1 ] . ex vivo light microscopy ( lm ) of the right cornea performed using special stains for colloidal iron and masson 's trichrome failed to show the crystalline deposits [ fig . tem of a corneal biopsy specimen obtained during the operation showed needle - shaped crystalline deposits within keratocytes in corneal stroma of the right eye [ fig . sequencing analysis identified three known single nucleotide variants ( snvs ) and two novel mutations in exon 11 of the ctns gene [ table 1 ] . corneal cystine deposition is observed as optical hyperreflectivity of right anterior one - third ( arrow ) , as shown by cross - sectional anterior segment optical coherence tomography 
 ex vivo light microscopy of the right eye ( a ) colloidal iron stain , ( b ) masson 's trichrome stain ( scale bar = 0.5 um ) electron micrographs of corneal stroma . note that crystalline deposits are also shown to be membrane - limited at higher magnification ( scale bar = 0.5 um ) the typical untreated child with cystinosis has a short stature , light complexion , rickets , and photophobia . anterior segment oct showed that the anterior one - third of the corneal stoma was hyperreflective , while the posterior two - third was not . the use of tem to demonstrate the presence of intracellular crystals within corneal keratocytes is a reliable diagnostic tool for cystinosis . in our case , tem showed square or oblong cystine deposits measuring 0.52 m in length . however , ex vivo lm did not show crystalline deposits in the cornea , while ex vivo tem did show a few such crystalline deposits . therefore , the degree of symptoms does not correlate with deposits in the cornea , and even a small amount of crystals can cause problems . topical cysteamine treatment has proven safe and efficient at dissolving corneal crystals in cystinosis patients ; it also relieves the symptoms of photophobia , blepharospasm , and ocular pain . although our patient had used topical cysteamine , he presented with severe photophobia and decreased visual acuity . therefore , penetrating keratoplasty was performed . the basic defect involved in cystinosis the gene for cystinosis ( ctns ) was mapped to chromosome 17p13 by linkage analysis , and then isolated . this gene contains 12 exons spanning 23 kb of genomic dna , and exons 312 are coding . ctns mutations result in either the complete abolition of or a reduction in cystine transport . the ctns gene product , cystinosin , comprises 367 amino acids , seven predicted transmembrane domains , a gy dipeptide for lysosomal targeting near the c - terminus , and eight potential glycosylation sites . cystinosin has homology with a 55.5-kda caenorhabditis elegans protein and the yeast protein ers1 , it facilitates cystine egress from lysosomes . at least 85 different ctns mutations have been reported in the human gene mutation database ( http://www.hgmd.org/ ) . in cystinosis , the most common ctns mutation is a 57-kb deletion in which the 3 border cuts into exon 10 . our patient lacked the 57-kb deletion , but sequencing analysis of all ctns exons revealed three known snvs located in intron 6 and exons 7 and 10 in the dbsnp ( http://www.ncbi.nlm.nih.gov/snp/ ) ( rs459613 , rs200313254 , rs161400 ) , and two novel mutations in exon 11 ( c. 854c > a , c. 943c > t ) . of the two novel gene mutations , one ( c. 943c > t ) resulted in an amino acid substitution ( p.gln315x ) , and the other ( c. 854c > a ) likely affected splicing during transcription because of its location near a predicted acceptor splice site , which would result in an abnormal splicing . as demonstrated in our patient , tem and anterior segment oct are useful to make a diagnosis of ocular cystinosis .
a 22-year - old man diagnosed with nephropathic cystinosis at the age of 4 years was found to have progressive bilateral corneal crystal deposition . 
 he presented with severe photophobia and decreased visual acuity . 
 ocular cystinosis was diagnosed on observing the typical crystals . 
 optical coherence tomography showed multiple areas of stromal hyperreflectivity due to crystal deposits within the corneal stroma . 
 ex vivo transmission electron microscopy of the cornea showed pathognomonic crystal deposits in corneal stromal keratocytes . using polymerase chain reaction sequencing of the entire coding region 
 , we identified five gene mutations , including two unreported mutations .