A 2-year-old boy with redness and hazy vitreous in the right eye was referred to our clinic. The patient underwent bilateral cataract surgeries 1 year ago. A review of the surgical recording and ultrasound revealed previous total cataracts, as well as whitening of nuclei in the cortex of both eyes. One month ago, in the cataract clinic, his mother reported redness and blurred vision in his right eye, and endophthalmitis was suspected.
Ophthalmic examination under anesthesia revealed normal intraocular pressure in both eyes (11 mmHg OD and 12 mmHg OS). The right eye had combined ciliary and conjunctival congestion, generally clear cornea, absent lens, and opacified vitreous. Ultrasonography demonstrated multiple hyperechogenic dots in the anterior chamber and vitreous opacity, indicating inflammation (Figures 1A,B). Wild-field fundus photography revealed a congested optic nerve head through the opacified vitreous (Figure 1C). Fluorescein angiography showed the retinal capillaries and hyperfluorescent optic disc leakage at the venous phase (Figure 1D). A single dose of combined vancomycin (1 mg/0.1 ml), ceftazidime (2.2 mg/0.1 ml), and dexamethasone (0.5 mg/0.1 ml) was injected consequently into the vitreous cavity. The aqueous fluid was drawn and analyzed via metagenomic next-generation sequencing (mNGS). Based on a published protocol, this technology can detect 20,343 different types of microbes including bacteria, viruses, fungi, parasites, and other pathogens (Beijing Zhide Medical Laboratory Co., Ltd., an Illumina NextSeq platform). Briefly, the intraocular fluid sample was extracted and purified using a TIANamp micro DNA kit (TIANGEN, Beijing, P.R.C). Qualified DNA was applied to construct DNA libraries using the QIASeq  Ultralow Input Library Kit (QIAGEN, Hilden, Germany). Qualified libraries were sequenced on a NextSeq 550 platform (Illumina, San Diego, United States). After obtaining the sequencing data, high-quality data were generated after filtering out the adapter, low-quality, low-complexity, and shorter reads. Next, human reads were removed by mapping the reads to the human reference genome by SNAP software. The remaining data were aligned to the microbial genome database using Burrows-Wheeler alignment. However, the result was negative. Inflammatory factor analysis of the aqueous fluid found elevated levels of VEGF at 97.7 pg/ml (normal range 1-40), basic fibroblast growth factor (BFGF) of 4.9 pg/ml (normal range <1.0), interleukin (IL)-6 of 7524.5 pg/ml (normal range 1.0-50.0), vascular adhesion molecule (VCAM) of 11066.9 pg/ml (normal range 200-1,000), and IL-8 of 3023.1 pg/ml (normal range 0-20.0). Finding no obvious cause for the vitreous inflammation, a vitreous sample was collected via vitrectomy. The sample was cultured for bacteria and fungi, and T-SPOT and procalcitonin tests were conducted to rule out tuberculosis and sepsis. All the results came out negative.
The patient was generally well-developed with no obvious abnormality on systemic examination. The family history was not remarkable. A systemic evaluation was performed when a diagnosis of unilateral non-infectious uveitis was considered. The immunological and rheumatological evaluation was not contributory. However, urinalysis revealed proteinuria and microscopic hematuria. The patient was then transferred to the pediatric department for further diagnosis. Electron microscopic analysis of a renal biopsy showed mesangial proliferation and thickening of the glomerular basement membrane (Figures 2A,B). Based on the pathology, Alport disease was suspected. The patient was subjected to whole-exome sequencing (WES) using the HiSeq X Ten sequencing platform (Illumina, San Diego, California, United States) and by MyGenostics, as described previously. A deletion in the X chromosome (Xq22.3: NC_000023.11:g.(107681122_107683515)del) encompassing exon 1 of COL4A5 and exons 1 and 2 of COL4A6 (Figure 2C) was found, which was confirmed by multiplex ligation-dependent probe amplification (MLPA). No hearing abnormalities were detected by audiometry. The patient exhibited no signs of dysphagia; however, close follow-ups are advised for this young patient. The child's mother had neither microscopic hematuria nor ocular manifestation. A family pedigree chart of the patient is shown in Figure 3.
Oral prednisone was prescribed for uveitis, starting at 15 mg/day and was gradually tampered. One month after steroid treatment, inflammation in the vitreous cavity resolved. Congestion of the optic nerve head was resolved, as shown in fundus photography (Figure 2D). However, proteinuria and hematuria still existed.