Ocular Pathology

Newer Techniques Around the Horizon


Geeta K Vemuganti
School of Medical Sciences
University of Hyderabad

Ophthalmic Pathology, like all branches of pathology encompasses, the essential nature of disease, especially of the structural and functional changes in tissues that cause or are caused by disease. It has contributed significantly to the understanding of disease process including etiology, pathogenesis, morphology of the lesion, effects of the lesion on course and prognosis, complications, treatment and the dangers of treatment. The tissues removed during any surgical procedure are obviously a storehouse of information, however with the aim of salvaging the organ and its function and with the advent of newer modalities of treatment, the trend towards small biopsies demanding the information on diagnosis, genetics, prognostic factors etc has made ophthalmic pathology more challenging. In this era, newer tools form the armamentarium of diagnosing the diseases. The routine histopathology, histochemistry, immunohistochemistry, cytology are complemented by modern molecular techniques like PCR, ELISA, karyotyping, Western Blotting, In- Situ Hybridization, gene expression studies, proteomics, metabolomics and Multiplex Ligand specific Probe Amplifier techniques.

Today’s research is tomorrows application!. Some of these tools have directly influenced the diagnosis and treatment of various ocular diseases. These include diagnosis of ocular infections caused by HSV and other viral infections, mycobacterium tuberculosis, fungal agents, and bacteria from various ocular specimens by PCR, multiplex PCR, Interferongamma release assays (IGRA) (Quantiferon Gold), Elisa, genechips, rapid cultures etc with higher specificity and sensitivity. Infections involving uvea and retina pose specific challenges in diagnosis and treatment due to masquerading features as well as diagnosis. Eg Uveititis of infective and non infective origin is a huge challenge to clinicians hence judicious use of routine and specific tests based on high index of clinical suspicious is the key to accurate, cost-effective and timely diagnosis. Classification of lymphomas and leukemia are now done using WHO classification, which emerged from the consensus of opinion of hematopathologists, hematologists, oncologists, and geneticists and represents a revision of the prior classification to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition. Hence it is understandable that diagnosis of Ocular lymphomas would also follow the same and would dependant on results of various molecular tests done. Oculoadenexal lymphomas that affect the conjunctiva, uvea, orbit and vitreous pose additional challenges because of lesser amount of tissue, requirement of invasive procedures and poor accessibility.
Similarly, uveal melanomas are now classified on the basis of morphology, phenotype and genetic alterations (Chromosomes 3, 8 etc) into Class 1 tumors- with no or minimal risk of metastasis; and Class 2 tumors with higher risk of metastasis. What is interesting is that these tests can be done routinely from the tumor samples obtained from fine needle aspiration cytology of the uveal melanoma and through a cost effective simpler technique of Muliplex Ligand probe amplication.

The use of Next generation sequencing (NGS) wherein the entire human genome can be sequenced rapidly and cost-effectively has contributed significantly to understanding of genetic diseases eg mutational spectrum and genotypephenotype correlations of inherited retinal dystrophies, retinoblastoma and solid tumors. The chromosomal rearrangements and translocation are now being increasing identified in situ on tumor samples by fluorescence in
situ hybridization (FISH) specially in soft tissue sacromas where it has now considered as pathognomic feature of some tumors eg alveolar rhabdomyosarcoma and , solitary fibrous tumor Some of the promising areas where the transition from research to diagnosis is awaited is in area of other ocular tumors like conjunctival melanomas, sebaceous cell carcinoma and OSSN, morphometric studies using image analysis, and telepathology.

In summary a good and effective team work of clinicians pathologists geneticists, oncologists goes a long way in incorporating the newer technologies more precisely and in a cost effective manner.

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