RBP4
RBP4 has recently been linked to autosomal dominant form of anophthalmia. This form of anophthalmia has variable penetrance and a unique maternal inheritance effect that is rooted in pregnancy. Specifically, the disease only occurs when a mother and fetus both carry a RBP4 mutation which predisposes the fetus to vitamin A deficiency (a known environmental risk factor for anophthalmia) during pregnancy. If Vitamin A deficiency occurs during the first several months when the eye is developing, it may lead to anophthalmia. This form of anophthalmia is the first that may be intervened upon with vitamin A supplementation of retinyl esters during the first several months of pregnancy. This strategy exploits an RBP-independent pathway. Clinical research is underway. See RBP4 for more information. Other influential genes
SOX2 and RBP4 are not the only genes that can cause anophthalmia. Other important genes include OTX2, CHX10 and RAX. Each of these genes are an important in retinal expression. Mutations in these genes can cause a failure of retinal differentiation. OTX2 is dominantly inherited. Mutation effects vary in severity, and can include microphthalmia. BMP4 is also linked to anophthalmia, as well as causing myopia and microphthalmia. It is dominantly inherited. BMP4 interacts with the Sonic hedgehog (SHH) pathway and can cause anophthalmia. Environmental influence
Many environmental conditions have also been known to cause anophthalmia. The strongest support for environmental causes has been studies where children have had gestational-acquired infections. These infections are typically viral. A few known pathogens that can cause anophthalmia are Toxoplasma, rubella, and certain strains of the influenza virus.
Tuberculous meningitis, also known as TB meningitis or tubercular meningitis, is a specific type of bacterial meningitis caused by the Mycobacterium tuberculosis infection of the meninges—the system of membranes which envelop the central nervous system. Signs and symptoms
Fever and headache are the cardinal features; confusion is a late feature and coma bears a poor prognosis. Meningism is absent in a fifth of patients with TB meningitis. Patients may also have focal neurological deficits. Causes
Mycobacterium tuberculosis of the meninges is the cardinal feature and the inflammation is concentrated towards the base of the brain. When the inflammation is in the brain stem subarachnoid area, cranial nerve roots may be affected. The symptoms will mimic those of space-occupying lesions.Blood-borne spread certainly occurs, presumably by crossing the blood–brain barrier; but a proportion of patients may get TB meningitis from rupture of a cortical focus in the brain; an even smaller proportion get it from rupture of a bony focus in the spine. Pathophysiology
The pathophysiology of tuberculous meningitis involves bacterial invasion of the brain parenchyma meninges or cortex, causing the formation of small subpial foci. These foci, termed Rich foci, are necrotic and expand as the colonies within them multiply. Tubercle (focal) rupture in the subarachnoid space causes meningitis. Diagnosis
Diagnosis of TB meningitis is made by analysing cerebrospinal fluid  collected by lumbar puncture. When collecting CSF for suspected TB meningitis, a minimum of 1ml of fluid should be taken (preferably 5 to 10ml). The CSF usually has a high protein, low glucose and a raised number of lymphocytes.