case_images: PMC11765409_01
case_images: Slit-lamp photographs and Fourier-domain anterior segment optical coherence tomographs (FD-OCT) of the proband. Slit-lamp photographs of the right eye (A,B) and left eye (D,E) are also shown. Diffuse grayish-white opacities in the subepithelial and superficial stroma ((A,D); black arrows) and distinct refractile lattice lines spreading to the periphery ((B,E); magnified views are shown at the upper right) were observed in both corneas of the proband. FD-OCT images of the right eye (C) and left eye (F) are shown. Diffuse grayish-white opacities in the subepithelial and superficial stromal area (black arrowheads) and many distinct refractile lattice lines spreading to the periphery (green arrowheads) were observed.
case_images: genes-16-00076-g001.jpg
case_images: PMC11765409_01_genes-16-00076-g001.jpg
case_images: genes-16-00076-f001
case_images: Both of the proband's corneas exhibited an irregular surface and diffuse grayish-white deposits in the subepithelial and superficial stroma along with distinct refractile lattice lines spreading to the periphery (Figure 1A,B,D,E). Fourier-domain anterior segment optical coherence tomography (FD-OCT) (RTVue-100; Optovue Inc., Fremont, CA, USA) confirmed that the proband had thick central superficial stromal opacities (Figure 1C,F).
case_images: Slit-lamp photographs of the right eye (A) and left eye (B) of the proband are shown. Many distinct refractile lattice lines spreading to the periphery near to the limbus (green arrowheads) were observed (A). Dense, thick lattice lines are seen in the mid-peripheral cornea (B). Slit-lamp photographs using retro-illumination of the right eye (C) and left eye (D) show 35 lines in the temporal half OD and 33 in the nasal half OS. Many dot-shaped opacities (40 OD and 23 OS) under retro-illumination (red arrows) and distinct refractile lattice lines spreading to the periphery (green arrowheads) were observed in both corneas of the proband (magnified views are shown at the right upper corners).
case_images: genes-16-00076-g002.jpg
case_images: PMC11765409_01_genes-16-00076-g002.jpg
case_images: genes-16-00076-f002
case_images: The lattice lines of the proband were more numerous in the mid-periphery, reaching the limbus and visible with direct and retro-illumination (Figure 2A-D). Under retro-illumination, approximately 35 lattice lines were observed in the temporal half of the proband's right cornea, and approximately 33 lattice lines were seen in the nasal half of his left cornea (Figure 2C,D). Approximately 40 dot-shaped opacities were present in the proband's right cornea, and approximately 23 were present in his left cornea (Figure 2C,D).
case_images: Slit-lamp photographs and Fourier-domain anterior segment optical coherence tomographic (FD-OCT) images of genetically confirmed classic LCD heterozygotes ((A,D,G); 32-year-old) ((B,E,H); 43-year-old) ((C,F,I); 40-year-old). Diffuse grayish-white opacities in the subepithelial and superficial stromal area (black arrows) are shown (A-C). Distinct refractile lattice lines (green arrowheads), which are less confluent (15, 12, and 14 lines in each half cornea of (D-F)) and thinner than those of the proband, spreading to the periphery are observed (D-F). The dot-shaped opacities are less numerous than those of the proband (13, 9, and 5 dots in each (D-F)) (red arrows). FD-OCT images of heterozygotes show fewer lattice lines (green arrowheads), while diffuse grayish-white opacities in the subepithelial and superficial stromal area (black arrows) were observed at various depths (G-I).
case_images: genes-16-00076-g003.jpg
case_images: PMC11765409_01_genes-16-00076-g003.jpg
case_images: genes-16-00076-f003
case_images: Slit-lamp photographs of other genetically confirmed GCD2 heterozygotes. Granular deposits (yellow arrows) and linear deposits (red arrowhead) were observed in the corneas of 40-year-old (A), 38-year-old (B), and 37-year-old heterozygotes (C).
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case_images: genes-16-00076-f004
case_images: Genetic analysis results of TGFBI in the proband (A,C) and proband's mother (B,D). The nucleotides changed from normal sequence are shown in red highlight (A,B). The automatic reader reported a change of arginine to tyrosine in the proband (A) and a change of arginine to cysteine in the proband's mother (B). Partial nucleotide sequences of exon 4 of the TGFBI gene of the proband shows both C and T curves at 370 nucleotide (red star) and both C and A curves at 371 nucleotide (blue star) (C). Partial nucleotide sequences of exon 4 of the TGFBI gene of the proband's mother shows both C and T curves at 370 nucleotide (green star) (D).
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case_images: PMC11765409_01_genes-16-00076-g005.jpg
case_images: genes-16-00076-f005
case_images: Sanger sequencing of the proband showed two heterozygous changes in exon 4, c.370C>T and c.371G>A variants in TGFBI (Figure 5A,C). Sanger sequencing of the proband's mother revealed a heterozygous c.370C>T:p.(R124C) variant (classic LCD heterozygote), suggesting that the two variants were on different alleles, compound heterozygous, in the proband. (Figure 5B,D). Since the proband's father had passed away, no biologic specimen was available from him for sequencing.
case_images: Slit-lamp photographs of the proband's right eye before PTK (A) and after PTK of 30 mum and additional 10 mum ablations (B,C) performed sequentially on the same day. Since the surgeon could not determine the depth of opacities precisely before PTK, an additional 10 mum ablation was performed with a slit-lamp examination after the 30 microm PTK to remove opacities and still preserve as much of the posterior stroma as possible for future additional PTKs.
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case_images: PMC11765409_01_genes-16-00076-g006.jpg
case_images: genes-16-00076-f006
case_images: A 30 microm PTK was performed, and the effect was evaluated with a slit lamp in the operating room (Figure 6B). Because visually significant opacities remained, an additional 10 microm PTK was performed to remove them (Figure 6C).
case_images: Slit-lamp photographs (OD) of the proband 1 month (A) and 6 months (B) after PTK. FD-OCT images taken 1 month after treatment show that superficial opaque deposits in the superior half were removed while some opacities remained in the inferior half of the right eye inside the white dotted oval line ((C), OD). Intact superficial opaque deposits remained inside the white oval line in the left eye, where PTK was not performed ((D), OS). The '# of averages' in the FD-OCT photo refers to the number of repeated scans and automatic averaging performed by the machine as part of its noise-reduction function. The photopic contrast sensitivity testing of the right, the treated eye, of the proband 1 month after PTK showed normal values at 1.5 cycles/degree and slightly low values at other frequencies (E). In contrast, the left eye showed very low contrast sensitivity at all spatial frequencies (F).
case_images: genes-16-00076-g007.jpg
case_images: PMC11765409_01_genes-16-00076-g007.jpg
case_images: genes-16-00076-f007
case_images: Slit-lamp photographs and an FD-OCT image 1 month after PTK confirmed the removal of superficial opaque deposits (Figure 7A,C), but deeper linear opacities that could be seen by retro-illumination remained in the mid-periphery about 230 microm from the posterior corneal surface. Contrast sensitivity testing was performed on both eyes 1 month after PTK (Figure 7E,F).