*2.6.3.3 Ophthalmic ultrasonography*

During the EUA, ultrasound imaging of both eyes can be used to assess the orbit for extraocular extension, to measure thickness of the lesions, and to obtain axial lengths of the eyes to evaluate for normal size and symmetry. Ophthalmic ultrasound has traditionally been used for diagnosing and monitoring treatment of retinoblastoma and distinguishing it from simulating lesions [20, 21]. As described previously in the chapter, a 10 mHz transducer in the A and B scan mode should be used to image the posterior pole and evaluate the size and location of tumors, evaluate for retinal detachment, and look for extraocular extension of tumor (**Figure 8**). Ultrasound is especially useful in cases when ophthalmoscopy is limited by a poor view or in presence of a cataract. As described previously in this chapter, large retinoblastoma lesions undergo dystrophic calcification from necrosis, and these can be readily observed as areas of hyper-reflection with acoustic shadowing.

## *2.6.3.4 Ultrasound biomicroscopy*

Ultrasound biomicroscopy (UBM) can also be helpful for visualizing the iris, pars plana, pars plicata, and ciliary body during an EUA. It is extremely helpful to

**35**

injection site.

**Figure 8.**

**Figure 7.**

*plane of the retina.*

*2.6.3.5 Electroretinogram*

*calcifications and acoustic shadowing.*

*Retinoblastoma: Presentation, Evaluation, and Diagnosis DOI: http://dx.doi.org/10.5772/intechopen.85744*

assess the anterior extent of tumor burden or to obtain more information regarding the pars panna and ciliary body as well as anterior chamber seeding. It is especially important to use UBM to rule out pars plana tumor involvement in cases where intravitreal injections of chemotherapy are being considered to choose a proper

*10 mHz B-scan ultrasonography of the left eye showing treated intraocular retinoblastoma with intrinsic* 

*(A) A portable wide field photograph showing a simulating lesion of retinoblastoma in the right eye showing a white macular lesion, close attention to the far periphery shows vascular telangiectasia and non-perfusion and (B) accompanying fluorescein angiogram confirming diagnosis of Coat's disease in 8 year old boy, again notice vascular telangiectasias and non-perfusion within a single* 

Electroretinograms (ERG) has been used to monitor retinal function before, during, and after therapy with intra-arterial chemotherapy. It is especially helpful in preverbal children who are unable to describe their level of visual function during the treatment course. Also it provides information regarding the cumulative effects of retinal damage secondary to therapy, chemotherapy toxicity, and tissue destruction from treatments including radiation, laser photocoagulation, and cryotherapy. During the EUA, a 30-Hz flicker has been tested and shown to be

### **Figure 7.**

*Retinoblastoma - Past, Present and Future*

**Figure 6.**

*2.6.3.3 Ophthalmic ultrasonography*

*2.6.3.4 Ultrasound biomicroscopy*

differentiate RB from simulating lesions. Firstly, subclinical neovascularization of the iris (NVI) can be distinguished using Retcam FA. In a recent study, eyes with advanced retinoblastoma, NVI was documented appearing as placoid or patchy areas of hyper fluorescence involving one or more sectors of the iris [19]. This finding typically occurred between 1 and 2 min. Retinoblastoma in the fundus should show dilated and tortuous vessels, with retinal arteries which "feed" the tumor of the largest caliber. Also, microaneurysms, retinal hemorrhages, and arteriovenous shunts can also be noted. In the same study, as the tumors enlarged, the abnormal vascularization was no longer consistent with normal retinal anatomy, and were contained entirely within the tumor itself. Intrinsic vessels of the tumor had disorganized and complex branching patterns, irregular caliber, and terminated early within the body of the tumor. This multi-level involvement of vascular abnormality helps the clinician readily distinguish RB from Coat's disease which has large dilated vessels which remain within one level of the retina and show extensive peripheral non-perfusion (**Figure 7A** and **B**). Lastly, after 3 min diffuse leakage from retinal vessels can lead to inability to discern fine details of the fundus, so the clinician should try to obtain all valuable information within the first 3 min of the study.

*(A) RetCam photograph of the left eye showing class D retinoblastoma prior to intra-arterial chemotherapy and (B) RetCam photograph of the left eye showing class D retinoblastoma after intra-arterial chemotherapy.*

During the EUA, ultrasound imaging of both eyes can be used to assess the orbit for extraocular extension, to measure thickness of the lesions, and to obtain axial lengths of the eyes to evaluate for normal size and symmetry. Ophthalmic ultrasound has traditionally been used for diagnosing and monitoring treatment of retinoblastoma and distinguishing it from simulating lesions [20, 21]. As described previously in the chapter, a 10 mHz transducer in the A and B scan mode should be used to image the posterior pole and evaluate the size and location of tumors, evaluate for retinal detachment, and look for extraocular extension of tumor (**Figure 8**). Ultrasound is especially useful in cases when ophthalmoscopy is limited by a poor view or in presence of a cataract. As described previously in this chapter, large retinoblastoma lesions undergo dystrophic calcification from necrosis, and these can be readily

Ultrasound biomicroscopy (UBM) can also be helpful for visualizing the iris, pars plana, pars plicata, and ciliary body during an EUA. It is extremely helpful to

observed as areas of hyper-reflection with acoustic shadowing.

**34**

*(A) A portable wide field photograph showing a simulating lesion of retinoblastoma in the right eye showing a white macular lesion, close attention to the far periphery shows vascular telangiectasia and non-perfusion and (B) accompanying fluorescein angiogram confirming diagnosis of Coat's disease in 8 year old boy, again notice vascular telangiectasias and non-perfusion within a single plane of the retina.*

#### **Figure 8.**

*10 mHz B-scan ultrasonography of the left eye showing treated intraocular retinoblastoma with intrinsic calcifications and acoustic shadowing.*

assess the anterior extent of tumor burden or to obtain more information regarding the pars panna and ciliary body as well as anterior chamber seeding. It is especially important to use UBM to rule out pars plana tumor involvement in cases where intravitreal injections of chemotherapy are being considered to choose a proper injection site.

#### *2.6.3.5 Electroretinogram*

Electroretinograms (ERG) has been used to monitor retinal function before, during, and after therapy with intra-arterial chemotherapy. It is especially helpful in preverbal children who are unable to describe their level of visual function during the treatment course. Also it provides information regarding the cumulative effects of retinal damage secondary to therapy, chemotherapy toxicity, and tissue destruction from treatments including radiation, laser photocoagulation, and cryotherapy. During the EUA, a 30-Hz flicker has been tested and shown to be informative prior to the physical examination portion of the exam [22]. One must be cautious to not manipulate the eyes before obtaining the ERG, as ocular manipulation including scleral depression, photography, and ophthalmoscopy can affect the ERG readings thus confounding results [23].

#### *2.6.3.6 Imaging for retinoblastoma*

Historically computerized tomography (CT) scans were used to evaluate patients ocular, orbital, optic nerve, and brain involvement from the tumor, since CT detection of calcifications in retinoblastoma have a sensitivity of 81–96% and an even higher specificity [24]. Magnetic resonance imaging (MRI) however is currently considered to be of higher accuracy and value due to its superior soft-tissue contrast for determining extent of tumor into orbit, optic nerve, and for evaluation of the presence of pinealoblastoma in trilateral disease. CT scanning is also felt to unnecessarily increase patient exposure to ionizing radiation with limited diagnostic value now that MRI is available. MRI of the brain and orbits with and without contrast is now ordered routinely on all patients with retinoblastoma at the time of diagnosis. The general practice among groups in the United States is to repeat imaging every 6–12 months for germline cases until the age of 5–6 years old to screen to pineal tumors. Transaxial or sagittal T1-weighted images will reveal an RB tumor which is slightly hyperintense with respect to the vitreous body. Transaxial or sagittal heavily T2-weighted imaging provides a low signal intensity of retinoblastoma and is helpful for detecting retinal detachment. Transaxial and sagittal oblique contrast enhanced T11 weighted spin echo provides information of the enhancement of retinal, invasive optic nerve, invasive eye wall, and anterior segment lesions.

#### *2.6.3.7 Genetic counseling*

After all of the steps outlined in this chapter are followed, and a diagnosis of retinoblastoma is made, the clinician can hold a discussion with the family regarding therapeutic options and the genetic counseling needed for the patient and their loved ones. A treatment plan can be devised and initiated, but is outside the scope of this chapter, and will be covered in other portions of this text.

## **3. Conclusion**

Accurate and consistent diagnosis of retinoblastoma, and it's simulating lesions begin with the initial consult. This involves a systematic approach starting with a detailed history and high level of suspicion for patients presenting with leukocoria, decreased vision, strabismus, periorbital swelling, or dysmorphic facial features. Initial examination should involve a detailed dilated fundus exam with ophthalmic ultrasound, which will either push the clinician towards or away from the diagnosis of retinoblastoma. Any suspicion should warrant an examination under anesthesia as outlined above to obtain all of the information needed for an accurate diagnosis. The examination under anesthesia should follow a consistent, careful, and repeatable fashion as described earlier in the chapter. The techniques above, if followed, should aid the clinician in consistent diagnosis of retinoblastoma and its simulating lesions. Once diagnosed, appropriate brain and body imaging, and referral for genetic counseling should be performed. Treatment of this rare condition, along with survival and preservation of the eye is continuing to improve and will be covered in other portions of this text.

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**Author details**

provided the original work is properly cited.

Spencer T. Langevin and Brian P. Marr\*

*Retinoblastoma: Presentation, Evaluation, and Diagnosis DOI: http://dx.doi.org/10.5772/intechopen.85744*

many of the photographs used in this chapter.

The authors would like to thank David McMahon for his assistance in obtaining

The authors have no conflicts of interests to declare in the production of this

**Acknowledgements**

**Conflict of interest**

book chapter.

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Harkness Eye Institute Columbia University, New York, NY, USA

\*Address all correspondence to: bpm2133@cumc.columbia.edu
