Fall 2017 Newsletter

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Fall 2017 Newsletter
7th Residency Announcement

Exciting Residency Announcement!

ACGME approves seventh resident complement; first increase in over 30 years!

Grand Rounds

Grand Rounds and Case Studies

Check out our weekly presentations



USC Ophthalmology Researchers Find More
Effective Treatments For Blinding Eye Diseases


Case Study: Dots in the Sky

Mustafi Rodger
Presenter: Debarshi Mustafi, MD, PhD Discussant: Damien Rodger, MD, PhD


  • 50-year-old female had been experiencing blurry vision in both her eyes for three to four months
  • No other significant past ocular history

Exam Findings

  • BCVA OD 20/25, OS 20/20, IOP normal in both eyes, no pupil abnormalities
  • Anterior segment slit lamp exam was normal
Figure 1
Figure 1: Dilated fundus exam was notable for vitreous cells and condensation. The vitreous cells were noted in a sheet-like appearance more in the right compared to the left eye.
Figure 2
Figure 2: OCT showed preservation of the retinal layering, but marked vitreous debris obscuring the signal.
Figure 3
Figure 3: Fluorescein angiography showed questionable mild vascular leakage.
Figure 4
Figure 4: Ocular ultrasonography revealed vitreous opacities and mobile membranes. There were areas of hyperechogenicity and mild irregularity of the choroidal wall without any obvious elevations.


Differential Diagnosis

  • Intermediate Uveitis
    • Sarcoidosis
    • Lyme disease
    • Multiple sclerosis
    • Intraocular lymphoma
    • Pars planitis
  • Chorioretinitis with vitritis
    • Behcet disease
    • Toxoplasmosis
    • Toxocariasis
    • CMV retinitis
    • Tuberculosis
    • White dot syndromes

Additional Investigations

  • Previous lab work was carried out to reveal:
    • HLA-B27, HLA-B51, HLA-A29-Negative
    • RPR/FTA-ABS-Negative
    • Quantiferon Gold-Negative
    • ACE-Negative
    • ANA-Negative
    • CMV/VZZ/HSV Serologies-WNL
    • Toxoplasmosis-Negative
  • Past medical history revealed that five years prior patient had underwent biopsy for a friable mass of her uterus due to abnormal vaginal bleeding
    • Prior Prior biopsy revealed: Diffuse infiltrates of large atypical lymphoid cells that expressed markers CD45, CD20, CD79a, PAX-5, MUM-1, BCL-6. These were consistent with diffuse large B-cell lymphoma
    • Patient underwent hysterectomy and systemic chemotherapy over a four month span five years ago
    • Patient had a PET-CT scan a few months prior to presentation demonstrating no suspicious uptake
  • Given that the laboratory work up was negative for any infectious or inflammatory markers, a diagnostic pars plana vitrectomy was carried out and showed the following:
Figure 5
Figure 5: Vitreous biopsy revealed large lymphocytes with hyperchromic chromatin, nuclei that vary in size, and scant cytoplasm (left panel). These cells were CD20 positive (middle panel) and CD3 negative (right panel).
Figure 6
Figure 6: Stains (left to right) for IRF4/MUM1, PAX5, BCL6, and BCL2 were all positive.
  • Repeat full body PET-CT revealed hypermetabolic subcentimeter bilateral cervical and hypermetabolic and enlarged bilateral axillary lymph nodes concerning for malignancy


  • The vitreous biopsy showed abnormal lymphocytes staining positive for markers CD20, PAX-5, MUM-1, BCL-6, BCL-2, (CD3 negative) consistent with intraocular diffuse B-cell lymphoma with PET-CT demonstrating metastatic disease


  • Diffuse large B-cell lymphoma is the most common form of adult non-Hodgkins lymphoma and is the most frequent lymphoma subtype arising in the eye
  • The incidence of intraocular lymphoma represents less than 2% of ocular malignant tumors with overall incidence of 0.47 cases per 100,000 people per year
  • Median age of disease is 50-60 years
  • Ocular disease is bilateral in up to 80% of cases
  • Most common presenting symptoms are:
    • Blurred vision
    • Reduced vision
    • Floaters
  • Most common clinical signs are:
    • Vitreous haze
    • Cells that can be seen in sheets or clumps


  • Treatment modalities include:
    • Intravitreal chemotherapy (methotrexate, rituximab)
    • Systemic and intrathecal chemotherapy
    • Radiotherapy (ranging from 30 to 50 Grays)
  • Treatment depends on level of systemic involvement

Prognosis and Future Directions

  • Prognosis depends on whether CNS is involved, histopathologic type (worse for T cell types), treatment opportunity, and whether it represents metastatic disease or primary disease
  • The delay between positive diagnosis and onset of ocular or neurological symptoms can be four to 40 months in primary intraocular lymphoma cases
  • Vitrectomy samples can be negative due to scarcity of cells-then chorioretinal biopsies may be required
  • Gene expression profiling has provided prognosis and treatment regimens:
    • Characterized by CD79a+, CD20+, PAX5+, BCL2+, IRF4/MUM1+, OCT2+, BOB.1+, BCL6+/-, CD10-/+
    • Co-expression of BCL6 and IRF4/MUM1 by CD20 positive cells in a vitreous biopsy is suggestive that B-cells are malignant
    • Staining of Ki-67 usually indicates high tumor cell growth
  • This patient’s disease is due to metastasis from previously treated lymphoma, likely finding safe harbor in the ciliary body for several years due to the unique vascularity of the tissue and relative immune privilege


  • Akpek et al., Elevated vitreous interleukin-10 level is not diagnostic of intraocular-central nervous system lymphoma. Ophthalmology 106: 2291-2295, 1999.
  • Coupland SE. Molecular pathology of lymphoma. Eye 27: 180-189, 2013.
  • Hoang-Xuan K et al., Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology. Lancet Oncol, 16: e322-e332, 2016.
  • Kim et al., Survival outcomes of primary intraocular lymphoma: a single-institution experience. Am J Clin Oncol., 39: 109-113, 2016.
  • Korfel A and Schlegel U. Diagnosis and treatment of primary CNS lymphoma. Nat Rev Neurol 9: 317-327, 2013.
  • Sen HN, et al., Primary intraocular lymphoma: diagnosis and differential diagnosis. Ocul Immunol Inflamm, 17: 133-141, 2009.
  • Tang L-J, Gu C-L, Zhang P. Intraocular lymphoma. Int J Ophthalmol., 10: 1301-1307, 2017.


Section Editors


Produced by: Monica Chavez, John Daniel, Joseph Yim and Dr. Vivek Patel
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