Choroidal ruptures after adjuvant intravitreal injection of bevacizumab for aggressive posterior retinopathy of prematurity.

In recent times, laser treatment combined with intravitreal bevacizumab (Avastin) has been used rarely as early investigations to treat patients with aggressive posterior retinopathy of prematurity (ROP). We describe choroidal ruptures that were documented at 10 weeks after this combined treatment in a preterm infant born at 28 weeks gestation with a birth weight of 1190 g. Aggressive posterior ROP was diagnosed at the age of 6 weeks. Initial treatment included bilateral laser ablation, followed immediately by intravitreal bevacizumab (IVB, 0.75 mg) in the right eye. On day 5, a remarkable regression of plus sign and fibrovascular proliferation was noted only in the right eye. At this point, additional laser treatment combined with IVB was given in the left eye, which dramatically resolved plus disease and neovascularization. At 10 weeks after IVB in the left eye, two sites of choroidal ruptures were revealed along the posterior edges of laser scars. There was no evidence of choroidal neovascularization associated with the choroidal ruptures. Choroidal rupture may occur shortly after laser ablation plus IVB treatment for aggressive posterior ROP. This occurrence requires recognition to determine whether it is actually related to the treatment. Long-term follow-up is important for understanding the nature and progression of this potentially serious complication.

Value of electrodiagnostic assessment in nonsyndromic microcephaly.

PURPOSE: To evaluate the value of electroretinogram (ERG) and visual evoked potentials (VEP) in children with nonsyndromic microcephaly. METHODS: In this observational case series, six children with nonsyndromic microcephaly aged 8.5 to 158 months were examined. Main outcome measures included the amplitude of the flash ERG (photopic, flickering, scotopic, and dark-adapted responses), the amplitude and latency of the VEP (flash or pattern-reversal stimulus), visual acuity, slit-lamp biomicroscopy, and indirect ophthalmoscopy. RESULTS: Three children demonstrated normal fundus appearances, ERG, and VEP responses: two in this group demonstrated poor vision and brain computed tomography in the third showed schizencephaly. The remaining three children demonstrated abnormal ERG with predominant reduction in photopic amplitudes. Retinal pigmentary granularities were detected in two children in this group, one of whom has poor vision, generalized brain atrophy, and 40% reduction in VEP amplitudes. CONCLUSIONS: Abnormal ERG is not uncommon among children with nonsyndromic microcephaly. Although cone photoreceptors are affected more than rods, this does not anticipate poor vision. It appears that defects in posterior visual pathway or developmental malformations of the brain should be responsible for poor visual function in nonsyndromic microcephaly.

Neodymium:YAG laser damage threshold of foldable intraocular lenses.

PURPOSE: To determine the energy level of the neodymium:YAG (Nd:YAG) laser that induced a 50% incidence of intraocular lens (IOL) damage in 5 foldable IOL materials. SETTING: Department of Ophthalmology, Siriraj Hospital Mahidol University, Bangkok, Thailand. METHODS: To simulate the condition within the capsular bag, an IOL was sandwiched between 2 rubber membranes. The front membrane had a central opening mimicking the anterior capsulotomy; the back membrane acted as the posterior capsule. The model was submerged in a water-filled chamber. The Nd:YAG laser with an automatic focus 150 microm beyond the focus of the aiming beam was used to perform a posterior capsulotomy. Three IOLs of each of 5 foldable IOL materials were tested. One type of poly(methyl methacrylate) (PMMA) was studied as a reference. The incidence of IOL damage at various energy levels was recorded. Linear regression analysis was used to determine the 50% incidence damage threshold. RESULTS: The 6 materials tested included 1 silicone lens (SI-40NB, AMO), 1 hydrophobic acrylic lens (MA60BM, Alcon), 3 hydrophilic acrylic lenses (Haptibag Ang, IOLtech; ACR6D, Corneal; H60M, Bausch & Lomb), and 1 PMMA lens (LX10BD, Alcon). The 50% incidence damage threshold values were 0.37 mJ, 0.54 mJ, 0.58 mJ, 0.52 mJ, 0.66 mJ, and 0.68 mJ, respectively. CONCLUSIONS: The 50% incidence damage threshold in all the IOLs was below the energy level normally used to perform a posterior capsulotomy in clinical practice. However, setting the laser at the lowest possible energy, focusing the laser beam beyond the posterior capsule, and performing the capsulotomy early should minimize the risk of IOL damage.

Leber's hereditary optic neuropathy in Thailand.

PURPOSE: To study the clinical features of Leber's hereditary optic neuropathy (LHON) in Thai patients as compared with patients in the United States, Europe, and other Asian countries. METHODS: The blood mitochondrial DNA of patients from 19 Thai pedigree families was studied for LHON mutation by restriction enzyme analysis. RESULTS: Mitochondrial mutation at nucleotide position 11778 was detected in 37 affected patients and 21 unaffected maternal relatives. Ten of the 19 families were sporadic in transmission. The male preponderance in affected patients was 76%. The onset of visual loss ranged from 6 to 53 years of age (mean = 21.5 years). Of the 31 patients whose eyes were affected bilaterally, 48.4% developed visual loss simultaneously. Unilateral visual loss was found in 2 patients but 1 already had a blind eye resulting from trauma. Onset interval between eyes was up to 12 months (mean = 2.3 months). No associated heart disease or neurological disorder was detected in our pedigrees. Hyperemic disc, retinal telangiectasia, and tortuosity of vessels appeared on ophthalmoscopy in 29% of the patients. Final visual outcome was 0.1, or worse in 82.3%, with a mean follow-up period of 19.5 months. CONCLUSION: The clinical features of LHON in Thai patients are similar to those found in patients harboring the 11778 mutation in the United States, Europe, and Japan. However, although there is a male predominance in all populations studied, this is not so marked in the European and Thai populations.

Uveitis in a child: masquerade syndrome revisit.

We present a case of relapsing acute lymphoblastic leukemia (ALL) in the anterior chamber, uveitis masquerade syndrome, which was confirmed by anterior chamber paracentesis and aqueous fluid cytology. Three months previously, the patient developed anterior uveitis without hematologic relapse. The uveitis responded well to topical steroid. After anterior chamber paracentesis, bone marrow relapse was detected. High doses of chemotherapy were prescribed. Ocular radiation was planned but the patient developed septicemia and expired. In our opinion, paracentesis should be performed without delay when uveitis develops in ALL, regardless of systemic relapse. Ocular manifestation may be the only sign of leukemic relapse or may present several months prior to systemic relapse.

A unique 3.5-kb deletion of the mitochondrial genome in Thai patients with Kearns-Sayre syndrome.

Kearns-Sayre syndrome is one of the neurological diseases caused by a defect in the energy-producing system of mitochondria. Keams-Sayre is known to be associated with a deletion in the mitochondrial genome and is usually detected in muscle biopsies of the patients. In this study, we report the molecular lesion of mitochondrial DNA (mtDNA) in four Thai patients admitted to hospital with encephalomyopathies. The 3.5-kb deletion of mtDNA was detected by Southern analysis, mapped by amplification with five primer pairs covering almost the total mitochondrial genome, and confirmed by PCR primer shift analysis. The deleted position was localized to nt 10208/13765 or nt 10204/13761 spanning the coding area of subunits 3 (ND3), 4L (ND4L), 4 (ND4), and 5 (ND5) of respiratory chain enzyme complex I and the tRNA genes for histidine, serine, leucine, and arginine. The sequence flanking the deletion was a 4-bp repeat of TCCC. All four patients have exactly the same 3558-bp mtDNA deletion; this is the only deleted position in their mtDNA but is different from those reported in the literature. The deletion seems to be found only in Thai patients, although they present with different clinical manifestations and none of them is not related.

Microcephaly with chorioretinal degeneration.

PURPOSE: To describe the ophthalmologic findings and electroretinograms in patients with microcephaly and chorioretinal degeneration. METHODS: We reviewed the hospital records of 20 patients with microcephaly that was not part of a recognizable syndrome prior to initial referral to the institutional consultative practice of one of the authors (RGW). Twelve patients, all from separate families, were diagnosed as having microcephaly with chorioretinopathy. Ten of these patients had ISCEV-standard electroretinograms (ERG). RESULTS: No family history of microcephaly or retinal degeneration was found in any of our patients. Three patients had another family member with mental retardation. Three of the 12 were compatible with the autosomal dominant form of microcephaly with chorioretinopathy (MIM 156590), possibly as a new mutation. Eight patients, who had fundus findings of retinitis pigmentosa, were similar to the autosomal recessive form of microcephaly with chorioretinal degeneration (MIM 251270). The ERGs were moderately to severely subnormal for responses of both rods and cones. The retinal findings varied from no pigmentary changes, pigment clumping and bone spicules, pigmentary granularity, bull's eye maculopathy, choroidal and retinal atrophy, to lacunar depigmentation. Mental retardation was mild to profound. The abnormal findings from MRI/ CT brain scans (8 patients) were cerebellar atrophy (2), agenesis of cerebellar vermis (1), cortical atrophy (1), and pachygyria (1). Dysmorphic features were present in most patients. Chromosome studies were normal, except for one patient with ring chromosome 14. CONCLUSIONS: Although the patients reviewed in this study represent a heterogeneous group of disorders, ocular abnormalities, especially retinal degeneration, are frequent among patients with microcephaly.

Eye findings in 8 children and a spontaneously aborted fetus with RSH/Smith-Lemli-Opitz syndrome.

We evaluate the ophthalmologic findings in 8 children with RSH/Smith-Lemli-Opitz syndrome (SLOS) and document abnormal concentrations of cholesterol and cholesterol precursors in the ocular tissues in a case of SLOS. The most common ophthalmologic finding was blepharoptosis, which was found in 6 of 8 patients, with the severity ranging from mild to moderate. None of the patients in the present study demonstrated cataracts; none had amblyopia from blepharoptosis. One patient had a right hypertropia with overaction of the inferior oblique muscle. This patient also had optic atrophy and a second patient had bilateral optic nerve hypoplasia. The importance of these findings to the visual function remains to be defined. Sterol analysis from ocular tissues of an aborted fetus with SLOS showed increased 7- and 8-dehydrocholesterol and a low cholesterol concentration in the retinal pigment epithelium, lens, cornea, and sclera. Routine ophthalmologic examination is indicated in SLOS because of the high incidence of abnormalities, most likely due to the abnormal synthesis of cholesterol and cholesterol precursors in the ocular tissues of these patients, as evidenced by sterol analysis of the ocular tissues in a case of SLOS.

Mitochondrial genome analysis in Kearns-Sayre syndrome.

We analysed the mitochondrial genome of one patient with chronic and progressive bilateral ophthalmoplegia. This patient also had abnormal EKG showing cardiac conduction defects and pigmentary retinopathy, suggestive of the Kearns-Sayre syndrome. On muscle biopsy, with Gomori trichrome stain, the fibers showed an increase in red-staining material in the intermyofibrillary network and the subsarcolemmal region. On electron microscopy, aggregations of abnormal mitochondria were demonstrated, confirming the diagnosis of mitochondrial myopathy. Analysis of mitochondrial DNA (mtDNA) from the patient and her mother showed no deleted mtDNA.